Preventing Osteoporosis and Reducing Fracture Risk

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Preventing Osteoporosis and Reducing Fracture Risk
Usman Malabu FACP, FRCPI, FRACP Staff Endocrine
Specialist Assoc. Prof. of Medicine The
Townsville Hospital James Cook
University Townsville, North Queensland -Australia
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Case Presentation

• 68 year old female Mrs. KY
• CXR for cough osteopenic bones

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Outline Management Plan

• What further history
• Clinical examination
• Investigations
• Treatment Prevention

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History Mrs. KY

• Hx of Prior Fractures
• Falls Hx
• Neurological D-Z Hx
• Hx of Muscular Weakness
• Nutritional Hx
• Medication Hx
• Functional Hx

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Nutritional History Mrs. KY

• Deficiency States
• Calcium
• Vitamin D
• Vitamin C

• Excess Intake
• Caffeine
• Alcohol
• Smoking

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Physical Examination Mrs. KY

• Orthostatics
• Gait Mobility
• Height
• Kyphosis
• Clinical Features of
• Hypercortisolism
• Hyperthyroid

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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
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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
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Hip
BMD
Spine
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WHO Definitions
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Bone Health
Normal
Osteoporotic
Bone quality is not the only factor
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Diagnosis of Osteoporosis

• History etiology and RFs
• Exam kyphosis, prox weakness
• X-rays fractures
• BMD bone mass
• Laboratory tests etiology, BTOM

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• After mid-30s slow loss
• Post-menopause rapid loss
• Men lose bone mass too.

Source The 2004 Surgeon Generals Report on Bone
Health and Osteoporosis What It Means to You at
http//www.surgeongeneral.gov/library/bonehealth
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The Domino Fracture Effect
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Fracture Risk Reduction

• Minimize over-zealous Rx of those at
  indeterminate risk

• Look for risk factors other than low bone mineral
  density

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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
• gt3 for hip fracture
• gt15 for major fractures

FRAX. Available at http//www.shef.ac.uk/FRAX/in
dex.htm.
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Prof. John A KanisUniversity of Sheffield
FRAX. Available at http//www.shef.ac.uk/FRAX/in
dex.htm.
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Risk factors
The red flags for osteoporosis risk.
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IDENTIFY RISK FACTORS OF OSTEOPOROSIS
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• Older than 65
• after age 50
• Underweight
• Previous falls
• FMH of Osteo/

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IDENTIFY RISK FACTORS OF OSTEOPOROSIS
2

• Smoking
• gt 2 drinks of alcohol/week

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• 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

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RISK FACTORS OF OSTEOPOROSIS MEDICATIONS
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• 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

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The good news Osteoporosis is preventable for
most people!

• Diet and lifestyle

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Management of Osteoporosis

• Prevention / Primary Prevention
• Lifestyle
• Diet
• Exercise
• Smoking
• Alcohol Intake
• Sunlight Exposure
• Pharmacological
• Drugs altering BMD
• Non-pharmacological
• Physiotherapy
• Hip Protectors

• Treatment / Secondary Prevention
• Lifestyle
• Diet
• Exercise
• Smoking
• Alcohol Intake
• Sunlight Exposure
• Pharmacological
• Drugs altering BMD
• Analgesia
• Non-pharmacological
• Physiotherapy
• Pain Relief
• Falls Assessment

Prevention of Falls
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Lifestyle Advice
Diet Balanced diet containing adequate
calcium 1000 mg/day
Exercise Regular weight bearing exercise 3 times
a week for 20 minutes minimum
Smoking Stop smoking
Sunlight Exposure 15-20 minutes on face, hands
and forearms twice weekly form April to October

• Alcohol
• Within safe limits
• 2u/day women
• 3u/day men

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Calcium Rich Diet Vitamin D Prevent
Falls Weight-Bearing Exercise
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Walking Dancing Gardening Tennis Jump
Rope Volleyball Skating
Activity Exercise Guide
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Dont Smoke Minimize Caffeine Alcohol Testing
Medication if Needed
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Calcium Requirements age related
Goal
500 mg 1,300 mg
http//www.osteoporosis.org.au/news/latest-news/ne
w-guidelines-released-in-mja-open/
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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 bones

RDI for older people 1300 mg
4.5 glasses of milk
http//www.racgp.org.au/download/documents/Guideli
nes/Musculoskeletal/racgp_osteo_guideline.pdf
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• Vitamin D for Ca absorption
• 400 IU daily
• Vitamin D is in milk (100 IU in 1 cup)

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Current treatments in OP

• Antiresorptive
• Estrogens and SERMs
• Calcitonin
• Bisphosphonates
• Denosumab
• Anabolic (stimulate bone formation)
• Parathyroid hormone
• Dual action agents
• Strontium ranelate

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Estrogen

• ERT increases BMD gt 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

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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 agedgt60)

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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

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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

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Calcitonin

• Calcitonin is effective for OP fracture pain
• Effect takes about 2 weeks.
• Silverman, SL. Osteoporos Int. Nov
  200213(11)858-867.
• No significant effect in the hip

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Bisphosphonates

• Binds to bone
• Inhibits osteoclast activity
• Supports osteoblast bone formation
• First line treatment for osteoporosis

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Bisphosphonates

• Alendronate (Fosamax) generic
• Risedronate (Actonel) better GI profile
• Ibandronate (Boniva) no hip protection
• Zoledronic Acid (Aclasta) once a year

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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
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5/10,000 risk gt 5 yrs Rx
Atypical
NEJM 36418 nejm.1730 org may 5, 2011
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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).
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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

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Parathyroid Hormone (PTH)

• Forteo (Teriparatide)
• 3rd line, use for 18 months
• Daily 20mg or 0.08ml SQ injection
• Intermittent antiresorptive effect
• Preferential osteoblastgtosteoclast activity

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PROLIA REAL WORLD
Factors influencing treatment
Efficacy
Adherence
Cost
Convenience/patient choice
Safety/tolerability
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Osteoporosis Prevention and Treatment
Hormonal Replacement
SERM
Treatment choice
PTH
Vitamin D
Life Style
20
40
60
80
Age
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Summary of Medications

• Bisphosphonates- First line therapy
• Must have GFR gt 30
• Denosumab, 2x/yr useful in low eGFR
• Strontium 3rd line C/I IHD
• PTH 3rd line use lt2yrs
• Estrogen for post-menopause symptoms
• SERM spine only

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OP When to refer to Specialist?

• Rx side effects
• Other complex medical conditions
• Inadequate response to Rx
• Vertebral fracture
• lt50 years
• Identified secondary cause
• Continue to with normal BMD

http//ebooks.adelaide.edu.au/dspace/bitstream/244
0/39778/1/hdl_39778.pdf
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Calcium/Vitamin D Controversies

• Ca/Vit D tablets harm/benefit

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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 9342d2040
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RESULTS
ANY Personal Calcium Use
NO Personal Calcium Use
Event CaD N8429 Placebo N8289 HR 95 CI P CaD N8429 Placebo N8289 HR 95 CI P
MI 209 168 1.2 (1-1.5) 0.05 180 196 0.92 (0.75-1.1) 0.44
CVA 196 163 1.2 (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
Bolland MJ et al. BMJ 2011 9342d2040
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Bolland MJ et al. BMJ 2011 9342d2040.
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Bolland MJ et al. BMJ 2011 9342d2040.
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Incidence of MI/CVA in Subjects on Calcium
Bolland MJ et al. BMJ 2011 9342d2040.
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Ca-VitD Incidence of Death
Bolland MJ et al. BMJ. 2010341c3691.
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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

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Calcium Risk of Death Men vs Women
Xiao Q et al. JAMA Intern Med. 2013173(8)639-46.

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Calcium Risk of Death Men vs Women
Xiao Q et al. JAMA Intern Med. 2013173(8)639-46
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Implication for Clinical Practice

• Recommendation for widespread use of Ca Rx no
  longer appropriate
• Calcium/vitamin D-rich diet favoured
• Further studies needed

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Bone Health Building Blocks
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Conclusion

• Osteoporosis is a growing epidemic
• Preach prevention!
• DEXA for all women gt65, and others
• Treat all elderly, and patients at risk, with
  diet-rich Calcium and Vitamin D
• Dont be afraid of bisphosphonates

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Thank You