Preventing Osteoporosis and Reducing Fracture Risk

Usman Malabu; FACP, FRCPI, FRACPStaff Endocrine Specialist & Assoc. Prof. of Medicine

The Townsville Hospital & James Cook University

Townsville, North Queensland -Australia

Case Presentation

68 year old female –Mrs. KY

CXR for cough: ‘osteopenic’ bones

Outline Management Plan

What further history

Clinical examination

Investigations

Treatment & Prevention

History: Mrs. KY• Hx of Prior Fractures

• Falls Hx

• Neurological D-Z Hx

• Hx of Muscular Weakness

• Nutritional Hx

• Medication Hx

• Functional Hx

Nutritional History: Mrs. KY

Deficiency States Calcium

Vitamin D

Vitamin C

Excess Intake Caffeine

Alcohol

Smoking

Physical Examination: Mrs. KY

Orthostatics Gait & Mobility Height Kyphosis Clinical Features of

Hypercortisolism Hyperthyroid

Evaluation for Suspected Osteoporosis in Selected Patients

Test Possible etiology Alkaline phosphates Osteomalacia

Calcium Vitamin D deficiency

Malabsorption

Hyperparathyroidism

Liver or kidney function Liver or kidney disease

TSH Hyperthyroidism

Total testosterone (men) Hypogonadism

25-hydroxyvitamin D Vitamin D deficiency

Complete blood count Multiple myeloma

Malabsorption

Evaluation for Osteoporosis in Selected Patients Test Possible etiology

FSH, LH, Estradiol (women) Hypogonadism

PTH Hyperparathyroidism

ESR, uBJP Multiple myeloma

CTX –bone turn over marker Assess activity of osteoporosis

Hip

Spine

BMD

WHO Definitions

Normal T score > -1 SD

Osteopenia -1 T score >-2.5 SD

Osteoporosis T score -2.5 SD

Established Osteoporosis T score -2.5 SD + low energy fracture

Normal Osteoporotic

Bone Health

Bone quality is not the only factor …Bone quality is not the only factor …

Diagnosis of Osteoporosis

History: etiology and RFs

Exam: kyphosis, prox weakness

X-rays: fractures

BMD: bone mass

Laboratory tests: etiology, BTOM

• After mid-30’s: slow loss

• Post-menopause: rapid loss

• Men lose bone mass too.

Source: The 2004 Surgeon General’s Report on Bone Health and Osteoporosis: What It Means to You at http://www.surgeongeneral.gov/library/bonehealth

14

The Domino Fracture Effect

Fracture Risk Reduction

Look for risk factors other than low bone mineral density

Minimize over-zealous Rx of those at indeterminate risk

Fracture Risk Assessment

Developed by WHO: FRAX

Enhances ability to predict fracture risk: BMI of femoral neck Clinical risk factors

ABSOLUTE RISK 10-year period >3% for hip fracture >15% for major fractures

FRAX™. Available at: http://www.shef.ac.uk/FRAX/index.htm.

FRAX™. Available at: http://www.shef.ac.uk/FRAX/index.htm.

Prof. John A Kanis

University of Sheffield

Risk factorsRisk factors

The “red flags” for osteoporosis risk.

Older than 65

# after age 50

Underweight

Previous falls

FMH of Osteo/#

1

IDENTIFY RISK FACTORS OF OSTEOPOROSIS

Smoking

> 2 drinks of alcohol/week

2

IDENTIFY RISK FACTORS OF OSTEOPOROSIS

RISK FACTORS: CURRENT OR PMH Cancer Chronic lung disease Chronic liver or kidney disease Inflammatory bowel disease Rheumatoid arthritis Hyperparathyroidism Vitamin D deficiency Cushing's syndrome Hyperthyroidism

3

One of these medicines: Oral glucocorticoids (steroids) TZDs –pioglitazone PPIs Cancer treatments (radiation, chemo) Thyroxine Antiepileptic medications –phenytoin, CMZ Gonadal hormone suppression -medroxyprog Immunosuppressive agents

4

RISK FACTORS OF OSTEOPOROSIS: MEDICATIONS

The good news: Osteoporosis is preventable for most people!

• Diet and lifestyle

Management of OsteoporosisTreatment / Secondary Prevention

Lifestyle Diet Exercise Smoking Alcohol Intake Sunlight Exposure

Pharmacological Drugs altering BMD Analgesia

Non-pharmacological Physiotherapy Pain Relief

Falls Assessment

Prevention / Primary Prevention

Lifestyle Diet Exercise Smoking Alcohol Intake Sunlight Exposure

Pharmacological Drugs altering BMD

Non-pharmacological Physiotherapy Hip Protectors

Prevention of Falls

Lifestyle AdviceDiet

Balanced diet containing adequate calcium

1000 mg/day

ExerciseRegular weight bearing

exercise 3 times a week for 20 minutes minimum

SmokingStop smoking

AlcoholWithin safe limits–2u/day women–3u/day men

Sunlight Exposure15-20 minutes on face, hands and forearms twice weekly form April to October

Calcium Rich Diet

Vitamin D

Prevent Falls

Weight-Bearing Exercise

Walking

Dancing

Gardening

Tennis

Jump Rope

Volleyball

Skating

Activity – Exercise Guide

Don’t Smoke

Minimize Caffeine & Alcohol

Testing & Medication if Needed

Calcium Requirements: age related

http://www.osteoporosis.org.au/news/latest-news/new-guidelines-released-in-mja-open/

500 mg 1,300 mg Goal

Dietary sources of calcium

• Dairy foods– Most readily absorbed Ca– Main source of calcium in

Australian diets– RDI = 3 serves per day

• Ca-enriched soy drinks• Fish with boneshttp://www.racgp.org.au/download/documents/Guidelines/Musculoskeletal/racgp_osteo_guideline.pdf

RDI for older people = 1300 mg

= 4.5 glasses of milk

CALCIUM

VITAMIN

•Vitamin D for Ca absorption

•400 IU daily

•Vitamin D is in milk (100 IU in 1 cup)

Current treatments in OP Antiresorptive

Estrogens and SERMs Calcitonin Bisphosphonates Denosumab

– Anabolic (stimulate bone formation) Parathyroid hormone

Dual action agents Strontium ranelate

Estrogen

ERT increases BMD > SERM Prestwood, KM et al. J Clin Enodocrinol Metab. 2000; 85(6): 2197-2202

WHI raised concerns about CV risks

E2 still approved for hot flashes

Low-dose ERT at menopause will delay bone thinning not as first-line therapy

HRT: A CONSENSUS

Prime role of HRT is relief of menopausal Sx

Risks/benefits: breast Ca 2-6/1000 women treated with HRT for 5 years

Use lowest effective E2 dose, assess CV risk

Review need annually (esp aged>60)

HRT: A CONSENSUS

Can give up to age 50 if prem menopause

Do not use in IHD/CVA, or Alzheimer's

Transdermal E2 has lower DVT risk

RALOXIFENE -SERMS

Reduces vertebral (not hip) fracture risk

Reduces development of new breast Ca

No increased risk of CVD (reduces CV events!)

Increased risk of DVT/PE & may worsen flushes

Well tolerated, easy dosing: 60 mg OD

Calcitonin

Calcitonin is effective for OP fracture pain

Effect takes about 2 weeks.Silverman, SL. Osteoporos Int. Nov 2002;13(11):858-867.

No significant effect in the hip

Bisphosphonates

Binds to bone

Inhibits osteoclast activity

Supports osteoblast bone formation

First line treatment for osteoporosis

Bisphosphonates

Alendronate (Fosamax) generic

Risedronate (Actonel) better GI profile

Ibandronate (Boniva) no hip protection

Zoledronic Acid (Aclasta) once a year

Unusual Complications of BisPO4s

Osteonecrosis of jaw-

Rare 1/100,000 patient years

94% in cancer patients receiving zoledronic acid or pamidronate

Woo S-B, et al. 2006 Ann Int Med 144(10):753-61

5/10,000; risk: > 5 yrs Rx

NEJM 364;18 nejm.1730 org may 5, 2011

Atypical #

Strontium ranelate

In women with postmenopausal osteoporosis:

Recent indication: Severe osteoporosis

3rd line used to be alternative to bisPO4s: elderly

if potential for GI complications

Beware rash (DRESS), VTE & MI

Contraindication: IHD, PVD, & CVA

MHRA Drug Safety Update 2013; 6(9).

Denosumab (Prolia)

Monoclonal Ab to RANKL which drives osteoclasts

Subcut every 6/12! 60mg

Dramatic and quick effect

Fracture reduction similar to Zoledronate

Used in renal failure

Parathyroid Hormone (PTH) Forteo (Teriparatide)

3rd line, use for 18 months

Daily 20mg or 0.08ml SQ injection

Intermittent antiresorptive effect

Preferential osteoblast>osteoclast activity

Factors influencing treatment

PROLIA®: REAL WORLD

Efficacy

Adherence Cost

Safety/tolerability

Convenience/patient choice

Osteoporosis Prevention and Treatment

Age

Hormonal Replacement

Bisphosphonates Strontium

SERM

20 40 60 80

Vitamin D

PTH

Life Style

Treatmentchoice

Summary of Medications Bisphosphonates- First line therapy

Must have GFR > 30

Denosumab, 2x/yr useful in low eGFR

Strontium 3rd line C/I IHD

PTH 3rd line use <2yrs

Estrogen for post-menopause symptoms

SERM: spine only

OP: When to refer to Specialist? Rx side effects

Other complex medical conditions

Inadequate response to Rx

Vertebral fracture

<50 years

Identified secondary cause

Continue to # with ‘normal’ BMD

http://ebooks.adelaide.edu.au/dspace/bitstream/2440/39778/1/hdl_39778.pdf

Calcium/Vitamin D Controversies

Ca/Vit D tablets –harm/benefit

Background

36, 282 postmenopausal WHI

1 G Ca + 400 IU VitD or Placebo for 7 years

Baseline: 20,000 on personal Ca Baseline: 16,000 no Ca

Bolland MJ et al. BMJ 2011 9;342:d2040

RESULTS

Event CaDN=8429

Placebo N=8289

HR 95% CI

P CaDN=8429

Placebo N=8289

HR 95% CI P

MI 209 1681.2(1-1.5) 0.05 180 196

0.92(0.75-1.1) 0.44

CVA 196 1631.2(0.9-1.4) 0.14 156 189

0.8(0.7-1) 0.08

MI/ CVA

386 326 1.16(1-1.4) 0.05 324 370

0.9(0.76-1) 0.09

NO Personal Calcium Use ANY Personal Calcium Use

Bolland MJ et al. BMJ 2011 9;342:d2040

Bolland MJ et al. BMJ 2011 9;342:d2040.

Bolland MJ et al. BMJ 2011 9;342:d2040.

Incidence of MI/CVA in Subjects on Calcium

Bolland MJ et al. BMJ 2011 9;342:d2040.

Bolland MJ et al. BMJ. 2010;341:c3691.

Ca-VitD Incidence of Death

Making Sense of the Results

1000 treated with Ca + Vit D for 5 years

MIs 4X Stroke 4X Death 2X 3 fractures would be prevented

Xiao Q et al. JAMA Intern Med. 2013;173(8):639-46.

Calcium: Risk of Death Men vs Women

Xiao Q et al. JAMA Intern Med. 2013;173(8):639-46

Calcium: Risk of Death Men vs Women

Implication for Clinical Practice

Recommendation for widespread use of Ca Rx no longer appropriate

Calcium/vitamin D-rich diet favoured

Further studies needed

Bone Health Building Blocks

Conclusion Osteoporosis is a growing epidemic

Preach prevention!

DEXA for all women >65, and others

Treat all elderly, and patients at risk, with diet-rich Calcium and Vitamin D

Don’t be afraid of bisphosphonates