OSTEOPOROSIS

CPD Presentation

by Chin Yeun, Shee (f0163)

Osteoporosis is defined as

‘a systemic skeletal disease characterised by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture.’

Figure 1: Representation of normal and osteoporotic bone tissue.

OsteoporosisAltered bone remodeling cycleAn imbalance in favor of bone resorption over bone formation

Osteoporotic bone shows an increase in the length of the remodeling cycle and reduced capacity to lay down a new mineralized bone matrix

Figure 2: Representation of the bone remodeling cycle in osteoporosis.Abbreviations: BRU, bone remodeling unit; CL, cement line; LC, lining cells; OS, osteoid.

From: www.medscape.com © 2010, Medscape.

Bone remodeling cycle consists of five phases:1. Activation: preosteoclasts are stimulated and differentiate under the influence of cytokines and growth factors into mature active osteoclasts;2. Resorption: osteoclasts digest mineral matrix (old bone);3. Reversal: end of resorption;4. Formation: osteoblasts synthesize new bone matrix;5. Quiescence: osteoblasts become resting bone lining cells on the newly formed bone surface.

ClassificationBased on individual bone mineral density (BMD)

Dual energy X-ray absorptiometry (DEXA) is the best current test to measure BMD Category Description

Normal BMD within 1 SD of young adult reference range(T score > -1)

Osteopenia BMD more than 1 SD but less than 2.5 SD below the young adult mean (T score between -1 and -2.5)

Osteoporosis BMD value of 2.5 SD or more below the young adult mean (T score ≤ -2.5)

Severe / Established Osteoporosis

BMD value of 2.5 SD or more below the young adult mean with the presence of 1 or more fragility fractures

Table 2: The World Health Organisation (WHO) criteria for classification of osteoporosis.Abbreviations: BMD, body mineral density; SD, standard deviation.

WHO Fracture Risk Assessment Tool: http://www.shef.ac.uk/FRAX/tool.jsp?country=35

Risk factorsNon-modifiable Modifiable

Older age (starting in the mid-30’s but more likely with advancing age)

Oestrogen deficiency (e.g. menopause)

Non-Hispanic white or Asian ethnic background Low calcium and vitamin D intake

Small bone structure or low body mass index (<19kg/m²) Sedentary (inactive) lifestyle or immobility

Family history of osteoporosis or an osteoporosis-related fracture in a parent or sibling

Cigarette smoking

Prior fracture due to a low-level injury, particularly after age 50 Excessive alcohol consumption

Medications

Long term treatment with glucocorticoids (e.g. prednisolone)Excess thyroid hormone replacement in patients with hypothyroidismHeparinTreatments that deplete sex hormones (e.g. anastrozole (Arimidex) and letrozole (Femara) to treat breast cancer or leuprorelin (Lupron) to treat prostate cancer and other health problems

Diseases

Endocrine (hormone) diseases (e.g. hyperthyroidism, hyperparathyroidism, hypogonadism, Cushing’s disease, osteogenesis imperfecta)Inflammatory arthritis (e.g. rheumatoid arthritis)Eating disorder (e.g. anorexia nervosa) Malabsorption / post-gastrectomyMultiple myeloma and malignancy

Table 1: List of possible risk factors of osteoporosis.

OsteoporosisMay not lead to any symptoms

Indicated when there is a broken (fractured) hip, wrist or spine after a minor fall

Often present with symptoms of back pain and potential loss of height and spinal (vertebrae) deformity, causing physical disable and even death

Figure 3: Progressive spinal deformity in osteoporosis

Management of Osteoporosis

Management of Osteoporosis in UMMC

Lifestyle interventions

Calcium intake

Vitamin D intake

Increase physical activity

Smoking cessation

Reduce alcohol consumption

From diet or supplements

Recommended Daily Calcium Intake

Category Age / year old Recommended Intake / mg

Neonates & Infants * 0 – 6 months7 – 12 months

200260

Children 1 – 34 – 89 – 13

700 1000 1300

Adolescents 14 – 18 1300

Men 19 – 5051 – 70

10001200

Women 19 – 5051 – 70 (Menopausal)

10001500

Elderly (men & women) Over 71 1200

Pregnant (Third trimester) & Lactating

14 – 1819 – 50

13001000

Table 3: Recommended daily calcium intake in different age groups.*Adequate intake

Sources of Calcium

Diet (e.g. milk, yogurt, cereal, soy beverages, and etc)

Supplementation

1. Calcium Carbonate

Recommended dose: 500 mg BD (May be sucked or chewed)

2. Calcium Lactate

Doses: Adults: 300-600 mg daily

Pregnant women (during 3rd trimester and lactation): 900-1200 mg daily

Children over 3 years: 300 mg daily

Note Patient may experience constipation, metallic taste or vomiting

after administer calcium lactate tablets. It is advised not to take within 2 hours of other oral medications upon administration of calcium lactate tablets.

Suggested Daily Vitamin D Intake

Adults

< age 50, 400 – 800 International Units (IU);

> age 50, 800 – 1000 IU

Sources of Vitamin D

Exposure under sunlight

Diet

(e.g. cod liver oil, milk, yogurt, salmon, egg, and etc)

Sources of Vitamin D (cont.)

Supplementation

Calcitriol and Alfacalcidol

Both are prescribed only for those who fulfill the requirements as below:

1. Renal impairment;

2. Patients > 65 years;

3. Intolerant to biphosphonates and SERMs;

4. Persistently low calcium levels;

5. Secondary hyperparathyroidism.

Sources of Vitamin D (cont.)

Supplementation

Active Vitamin D

Available forms

Dosages Prescribers

Calcitriol (or Rocaltrol)

0.25 mcg capsule

0.25 – 0.5 mcg daily (in divided doses – usually bd)

Orthopedics, Endocrinologists, Nephrologists, Geriatricians

Alfacalcidol 0.25 mcg capsule

1 mcg capsule

Initial dose: Adults & children > 20kg: 1 mcg daily; Children < 20 kg: 0.05 mcg/kg/day; Neonates: 0.1 mcg/kg/day

Maintenance dose: 0.25 – 2 mcg daily

Endocrinologists, Nephrologists

Table 4: The dosages of Calcitriol and Alfacalcidol.

The interrelationships between homeostatic hormones.

Schroeder N J , Cunningham J Nephrol. Dial. Transplant. 2000;15:460-466

© 2000 European Renal Association-European Dialysis and Transplant Association

Other supplement:

Metocal Vit D3

- A combination of calcium and vitamin D

- Dose: 1 – 2 chewable tablets daily

- Take at least 2 hr before or 2 hr after meals due to a possible decrease of iron absorption

Treatment options

Bisphosphonates (e.g. alendronate, risedronate)

SERM (e.g. raloxifene)

Calcitonin

Strontium ranelate

PTH treatment (e.g. teriparatide)

Bisphosphonates (also known as antiresorptive drugs)

Generic name

Brand name

Dosages Prescribers Notes

Alendronate Fosamax 70 mg once a week

Endocrinologist, Orthopeadics , O&G, Geriatricians, Rheumatologists

Patients must take on an empty stomach at least 30 minutes before breakfast with plain water only (allow optimal drug absorption) and remain upright for at least an hour after taking medications (bisphosphonates may irritate the esophagus).

Risedronate Actonel 35 mg once a week

Prof SP Chan, Dr Vijay, Dr Sargunan, Dr Lim Soo San, Dr Tai Cheh Chin, ProfVickneswaran, Prof Philip Poi, Prof Siti Zawiah Omar, Prof Tan Peng Chiong

Ibandronate Bonviva 150 mg once a month

Not prescribed in UMMC

Zoledronic acid

Aclasta Single IV infusion once a year

Lecturers and consultants of Orthopaedics, Endocrinology and Rheumatology

Patient must drink at least 2 glasses of water before infusion of drug. Postdose symptoms: fever,myalgia, flu like symptoms, arthralgia and headache (Usually occur within the first 3 days afteradministration of Aclasta).

Table 5: The available products of bisphosphonates and their dosages. Abbreviation: O & G, obstetrics and gynaecologists.

Selective oestrogen receptor modulator (SERM)

Mimics oestrogen’s good effects on bones without some of the serious side effects such as breast cancer

Decreases the risk of spine fractures, but there is a risk of blood clots with use of SERMs

Raloxifene (Evista)

Dose: 60 mg daily with or without food

Prescribers: Osteoporosis clinic: Prof SP Chan, Prof Rokiah, Dr Vijay; Orthopedic clinic: Dr Tai; Menopause clinic: Prof Siti Zawiyah

Calcitonin (Miacalcin)

A hormone made from the thyroid gland

Regulates calcium homeostasis

Prevents vertebral (spine) fractures and is helpful in controlling pain after an osteoporotic vertebral fracture

Nasal spray

Recommended dose: 200 IU / day

Injection

Dose: SC/IM 50-100 IU daily or every 2nd day.

Max supply: 5 days.

Prescribers: Endocrinologists or Orthopaedics

Common adverse effects: nausea, vomiting, dizziness, and flushing

Strontium Ranelate (Protaxos)

Stimulates bone formation and reduces bone resorption

Reduces fractures, but there is a risk of blood clots with use of this medication

In powder form; to dissolve 2g sachet in water and taken daily at bedtime, at least 2 hours after eating

Prescribers: Prof SP Chan, Dr Vijay, Dr Sargunan, Dr Lim Soo San, Dr Tai Cheh Chin, Prof Vickneswaran, Prof Philip Poi, Prof Siti Zawiah Omar, Prof Tan Peng Chiong

Parathyroid hormone (PTH) Treatment

PTH stimulates bone formation and activates bone remodeling, resulting in significant increases in bone mineral density and a reduction in fracture risk

Due to the potential risk of carcinogenicity (osteosarcoma) , recommended maximum duration of treatment is 18 months

Teriparatide Inj (Forteo) - Parathyroid Hormone AnalogDose: 20 mcg daily, into the thigh or abdominal wall (initial administration should occur under circumstances in which the patient may sit or lie down, in the event of orthostasis)Prescribers: Prof SP Chan, Dr Vijay, Dr Sargunan, Dr Lim Soo San, Ddr Tai Cheh Chin, Prof Vickneswaran, Prof Philip Poi, Prof Siti Zawiah Omar, Prof Tan Peng ChiongCommon adverse events: nausea, constipation, pain in limb, rashes, headache, sweating and dizziness

Management of Postmenopausal

Osteoporosis

Management of Glucocorticoid Induced

Osteoporosis

Management of Male Osteoporosis

ReferencesClinical Practice Guidelines on Management of Osteoporosis (downloaded in pdf form; Available from www.acadmed.org.my/view_file.cfm?fileid=208)

American College of Rheumatology website: http://www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/osteoporosis.asp

International Osteoporosis Foundation website: http://www.iofbonehealth.org/introduction-bone-biology-all-about-our-bones

D. Lajeunesse, J. –P. Pelletier, J. Martel – Pelletier (2010). Osteoporosis and Osteoarthritis: Bone is the Common Battleground. Medicographia. Vol. 32. No. 4. Page 391-398

Arthritis Foundation Malaysia website: http://www.afm.org.my/info/osteoporosis.htm

Websites:

a) http://www.webmd.com/osteoporosis/living-with-osteoporosis-7/causes

b) http://www.webmd.com/osteoporosis/living-with-osteoporosis-7/tests

c) http://www.uptodate.com/contents/search?search=osteoporosis&sp=0&searchType=PLAIN_TEXT&source=USER_INPUT&searchControl=TOP_PULLDOWN&searchOffset=

National Institutes of Health website: http://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/

MIMS Malaysia website

UMMC Online Formulary