Vietnam Osteoporosis Workshop, HCM Cty 2006

Secondary Osteoporosis

Tuan Van Nguyen and Nguyen Dinh NguyenBone and Mineral Research ProgramGarvan Institute of Medical Reseach

Sydney, Australia

Vietnam Osteoporosis Workshop, HCM Cty 2006

Overview

• Definitions

• Causes

• Corticosteroid Induced Osteoporosis:– Machanism– Magnitude of the problem– Patient managements

Vietnam Osteoporosis Workshop, HCM Cty 2006

Secondary osteoporosis

• Results from chronic conditions that contribute significantly to accelerated bone loss.

• Treatment of secondary osteoporosis is more complex than that of primary osteoporosis.

• Prognosis depends on the underlying disease.

Vietnam Osteoporosis Workshop, HCM Cty 2006

Secondary Osteoporosis

Endocrine or Metabolic causes

Medications

Collagen/genetics disorders

Nutritional disorders

Forms of secondary osteoporosis

Vietnam Osteoporosis Workshop, HCM Cty 2006

Endocrine or metabolic causes

• Hypogonadism• Hyperparathyroidism• Cushing-syndrome• Acidosis• Diabetes (type I)• Androgen insensitivity• Hemochromatosis• Gaucher’s disease

Vietnam Osteoporosis Workshop, HCM Cty 2006

Medications

• Corticosteroids

• Thyroid

• GnRH antagonists

• Anti-neoplastic agents

• Cyclosporin, methotrexate

• Phenobarbital

• Phenothiazines, Phenytoin

Vietnam Osteoporosis Workshop, HCM Cty 2006

Collagen/genetic disorders

• Ehler-Danlos syndrome

• Glycogen storage diseases

• Homocysturina

• Hypophosphatasis

• Marfan syndrome

• Osteogenesis Imperfecta

Vietnam Osteoporosis Workshop, HCM Cty 2006

Nutritional

• Alcoholism

• Calcium deficiency

• Chronic liver disease

• Gastric operations

• Malabsorption syndromes

• Vitamin D deficiency

Vietnam Osteoporosis Workshop, HCM Cty 2006

Corticosteroid-induced Osteoporosis (CIOP)

Vietnam Osteoporosis Workshop, HCM Cty 2006

Corticosteroid-induced osteoporosis

• CS used in many underlying diseases

• Benefits effects on the underlying disease vs. detrimental effects on bone.

• High percentage of osteoporosis and fracture

• Dose-dependent effect difficult to define

Vietnam Osteoporosis Workshop, HCM Cty 2006

CIPO-Epidemiology

• Prevalence of use of oral corticosteroids:– Population: 0.5%– Among women aged ≥ 55: 1.7%

L J Walsh et al, BMJ 1996;313:344-6

• Main indications:– Rheumatoid arthritis– Polymyalgia– COPD

• 14% of patients taking any treatment of osteoporosis

Vietnam Osteoporosis Workshop, HCM Cty 2006

CIPO: Burden

• Most common of drug-related osteoporosis in men and women

• Occur at any age, in both sexes, across races• Up to 50% patient of chronic steroid therapy sustain

osteoporotic fractures and/or develop osteonecrosis.• Significant bone loss can occur in as little as 3

months.• 50% chance of developing osteoporosis if on steroid

for 6 mo.

Vietnam Osteoporosis Workshop, HCM Cty 2006

Corticosteroids-effect on bone

Corticosteroids

Osteoblast

Inhibition

enhancement

Bone resorptionCalcium loss

increase

Calcium absorption

InhibitionInhibition

Gonadal hormone

Vietnam Osteoporosis Workshop, HCM Cty 2006

Who is at high-risk of CIPO?

Eastell R et al, J Intern Med 1998;244:271-92 Tobias JH, Rheumatology 1999;38:198-201

- Prior fracture- Premature menaupause at < 45y- Age > 65 y- Planned or current use CS > 6 mo- Low weight- Other causes of Osteoporosis

Vietnam Osteoporosis Workshop, HCM Cty 2006

CIPO and fractureR

elat

ive

risk

of

frac

ture

com

par

ed t

o c

on

tro

ls

0

1

2

3

4

5

6Non-vertebral Hip Vertebrae Forearm

Low dose(< 2.5mg/d)

Medium dose(2.5-7.5mg/d)

High dose(>7.5mg/d)

(Source: van Staa TP et al., 2000)

Vietnam Osteoporosis Workshop, HCM Cty 2006

Patient assessment

Eastell R et al, J Intern Med 1998;244:271-92

BMD measurement

BMD-Tscores? High-risk of CIOP?

>1 0 to -1.5 < -1.5 or with CS >15mg/dor with CS 7.5mg/d

x 6mo

-Thoracic and lumbar spine X-ray

-FBC, ESR & S-Electrophoresis if necessary

-Serum Ca, P, AP, Albumin

-Thyroid function

-Men: testosterone an women: FSH, LH

In 3-5 y

After 1 y

Lifestylemodification advice:

-Smoking

-Alcohol

-Physical activity

-Prevent fall

Vietnam Osteoporosis Workshop, HCM Cty 2006

CIOP-Management

• Primary prevention, PP (treatment started at the time initiation up to 3 mo of CS therapy)

• Secondary prevention, SP (treatment started >1y after the time initiation of CS therapy)

Vietnam Osteoporosis Workshop, HCM Cty 2006

Pharmacological therapyAgent PP SP Dose

Calcium &Vit D v v 1000mg/d & 50000U/w

Calcitrol v NA 0.6µg/d

Alfacalcidiol v NA 1µg/d

Calcitonin v NA Conflicting results (200U/d, nasal)

Fluoride v v 25mg BID plus Calcium

Etidronate v v marginal effect

Alendronate v v 5mg/d

Pamidronate v v Intermittent IV

Risedronate v v 5mg/d

HRT NA v

Testosterone (men) NA v

Vietnam Osteoporosis Workshop, HCM Cty 2006

Key messages

• Secondary osteoporosis is common

• Patients on CS therapy should be consider the need for therapy to prevent or treat CIOP

• Data on CIOP fracture reduction with treatment remain sparse

Vietnam Osteoporosis Workshop, HCM Cty 2006

Lời Cảm tạ

• Chúng tôi xin chân thành cám ơn Công ty Dược phẩm Bridge Healthcare, Australia là nhà tài trợ cho hội thảo.

Vietnam Osteoporosis Workshop, HCM Cty 2006

Thank you!