Preventing Osteoporosis and Reducing Fracture Risk Usman Malabu; FACP, FRCPI, FRACP Staff Endocrine...
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Transcript of Preventing Osteoporosis and Reducing Fracture Risk Usman Malabu; FACP, FRCPI, FRACP Staff Endocrine...
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
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
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
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
Older than 65
# after age 50
Underweight
Previous falls
FMH of Osteo/#
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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
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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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RISK FACTORS OF OSTEOPOROSIS: MEDICATIONS
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 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
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
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
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
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
Implication for Clinical Practice
Recommendation for widespread use of Ca Rx no longer appropriate
Calcium/vitamin D-rich diet favoured
Further studies needed
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