Prevention, Diagnosis and Treatment of Osteoporosis Stell

1
Prevention Diagnosis and Treatment of
Osteoporosis

• Stella Hayes MD
• CDR MC USN
• Geriatric Fellow
• East Carolina University
• (Home of the Pirates aaarrrgh)
• hayess_at_ecu.edu
• Special thanks to Irene Hamrick MD Geriatric
  Division Family Medicine Department Brody
  School of Medicine at ECU

2
Objectives

• Outline prevalence and cost of Osteoporosis
• Discuss preventive measures
• Learn whom to screen or test and how
• Review treatment options

3
Osteoporosis Epidemic

• Osteoporosis is a serious worldwide and growing
  health problem.
• More than 75 million people in Japan Europe and
  the U.S. have osteoporosis.

4
Osteoporosis Incidence

• 50 over 80 yo have osteoporosis
• Kanis et al. J Bone Miner Res 1994 91139
• 50 lifetime osteoporosis risk for women
• http//www.nof.org/osteoporosis/stats.htm
• The World Health Organization defines
  osteoporosis as having a T score of less than
  -2.5.

5
Thinning bones(Its just a matter of time.)

• BMD decreases with age.
• Osteoporosis (BMD lt -2.5 SD) increases with age

Kanis Melton Christiansen. Perspective The
diagnosis of osteoporosis. J Bone Miner Res 1994
91139
6
Kassem Melton Riggs. Involutional osteoporosis.
In Feldman Kelsay (eds) 1996. Osteoporosis. New
York Academic Press pp 691-702
7
Broken bones cost a bundle

• 40000 per hip fracture
• Osteoporosis International 19988(Supplement4)S7-
  80
• 17 billion osteoporosis
• 7.5 billion congestive heart failure
• 6.2 billion asthma
• Epstein S Goodman GR. Menopause 19996242-250

8
Osteoporotic Fractures Compared to Other Diseases
National Osteoporosis Foundation 2002. Available
at http//www.nof.org American Heart
Association. Heart Stroke Facts1999
Statistical Suppl. American Cancer Society.
Breast Cancer Facts Figures 1999-2000.
9
Osteoporotic fractures on the rise

• US AHRQ Report (Agency for Health Research and
  Quality)
• Hip other osteoporotic Fx increased by 55
• 55 per 100000 people in 1995
• 85 per 100000 people in 2006.
• http//www.ahrq.gov/news/nn/nn071709.htm
• (One more danger of the Silver Tsunami!)

10
Why are rates of Osteoporosis increasing

• We are living longer
• More illnesses and medications
• Soda caffeine alcohol tobacco salt
• Decreased Ca Vit D and exercise

11
Why are rates of Osteoporosis increasing

• Soda caffeine alcohol tobacco salt
• Decreased Ca Vit D and exercise

Modifiable Risk Factors
12
How we weaken our bones

• Caffeine- Increased urinary Ca excretion for 1-3
  hrs
• Alcohol- Decreases osteoblast activity
• Sodium- gt2 g/d increases Ca excretion
• Tobacco- Decreases estradiol
• Inadequate Ca and/or Vit D
• Inadequate exercise
• Use it or lose it

13
Preventing Osteoporosis

• Pay attention to your modifiable risk factors
  mainly what you put in your mouth!
• Anyone not taking in adequate dietary Calcium and
  Vitamin D should get supplements
• Dairy
• Fortified juice or soy milk
• Adequate calcium intake
• Lowers risk of kidney stone

14
Calcium Recommended Intake
http//ods.od.nih.gov/factsheets/calcium.asp
15
Calcium Absorption

• Absorption 6-20
• Food improves absorption by 20-25
• Heaney RP et al. Am J Clin Nutr. 1989 49(2)
  372-6
• Low stomach acid reduces absorption (Long term
  use of PPI correlated to low BMD)
• Only a small amount can be absorbed at one time
  so more frequent intake is better

16
Calcium supplements
17
Vitamin D Calcium Supplements
18
Vitamin D
19
Positive Effects of Vit D

• Increases Calcium absorption
• Strengthens Bones
• Reduces Falls
• - Increases muscle function decreases muscle
  pain and reduces body sway.
• Bischoff-Ferrari 2004 JAMA 291161999-2006
• Glerup H et al. 2000 J Int Med 247260-8
• Reduces Fractures
• As effective as Alendronate in cardiac transplant
  patients
• Alendronate 10 mg vs. Calcitriol 0.5 mcg daily
• Shane E et al. N Engl J Med. Feb 19
  2004350(8)767-776

20
Vitamin D

• Requirements increase with age
• 600 IU lt70 yo
• 800 IU gt70 yo
• IOM report 11/30/2010
• http//www.iom.edu/Reports/2010/Dietary-Reference-
  Intakes-for-Calcium-and-Vitamin-D.aspx
• In Osteoporosis give 1000 IU daily
• http//www.nof.org/prevention/vitaminD.htm

21
Exercise

• Back strengthening exercise lead to fewer
  vertebral fractures over 10 years
• 1.6 in exercising group
• 4.3 in control group
• Sinaki M et al. Bone 200230836-841
• Increased spine BMD over 9 months 3.5 vs. 1.5
• Villareal DT et al. JAGS 200351(7)985-90
• Kemmler W et al. Arch Int Med 2004164(10)1084-9
  1

22
Summary Break

• Osteoporosis is a growing epidemic
• Prevention through lifestyle modification is
  important
• Calcium and vitamin D are key
• Exercise

23
Whom to Test

• United States Preventive Services Task Force
  (USPSTF) Recommendation
• All women over 65
• Women over 60 with risk factors
• There are multiple risk factors
• Low body weight lt70 kg (154 lb) is the single
  best predictor of low BMD
• http//www.ahcpr.gov/clinic/uspstf/uspsoste.htm
  (2002)

24
Risk Factors

• Age
• Self-reported health
• Height
• Weight
• Hx of fracture after the age of 55 years
• Race/ethnicity
• Poor exercise

• Smoking
• Hx of parental fracture after the age of 40 years
• Diabetes treated with medications
• Rheumatoid Arthritis
• Corticosteroid use

Robbins J et al. 2007 JAMA 298(20)2389-2398
25
http//www.shef.ac.uk/FRAX/
26
DEXA

• Measures x-ray absorbed by calcium in bone
• Reported as
• T-score Compares with
• cohort of young adult
• Caucasian female BMD
• Z-score Age matched
• Gold standard
• Sensitivity 95
• Specificity 68

27
(No Transcript)
28
(No Transcript)
29
QUS vs. DEXA

• Pro
• Cheap (40 vs. 135)
• No ionizing radiation
• Readily available
• Hip Fx correlation
• (Bauer 1997 Hans 1996)
• Good for high or low BMD
• Sensitivity 94.1 Specificity 60.6

• Con
• Poor correlation with DEXA
• (Krestan 2001 Nayak 2006)
• Poor Precision
• Over time
• Between machines
• (Cummings 2002)
• Still need to get DEXA for most results
• Medicare pays only for 1 screening test q 2 years

30
Summary of Testing

• Scan all women gt65
• And other high risk women
• Scan every 2 years
• Less frequent if stable
• More frequent if changes anticipated
• Use DEXA
• Hip and spine lt70yo
• Hip and forearm gt70yo
• Use T-score
• Osteoporosis lt2.5
• Osteopenia/Low Bone Density lt-1.0- gt-2.5

31
Primary vs. Secondary Osteoporosis

• Women
• Primary osteoporosis
• 70-90
• Secondary osteoporosis
• 10-30

• Men
• Primary osteoporosis
• 36-50
• Secondary osteoporosis
• 50-64

Stein E Shane E. 2003 Metabolism Clinics of
North America 32115-34
32
Causes of Secondary Osteoporosis

• Tobacco
• Excess alcohol
• Vitamin deficiencies
• Vit D B12 Vit K
• Medications
• Anticonvulsants
• Steroids gt5mg/d for
• gt6 months

• Diseases
• Rheumatoid or other inflammatory arthritis
• Multiple myeloma lymphoma
• Hyperthyroidism
• Hyperparathyroidism

33
Tests to consider to r/o secondary osteoporosis

• 25-Hydroxy-Vitamin D3 Vit B12
• TSH
• PTH
• Testosterone (in men)
• Serum and urine Calcium
• Phosphate Cr LFTs
• CBC

34
Treatments- Medications

• Anabolic Agents
• Parathyroid hormone
• Sodium flouride
• Growth hormone
• Insulin-like growth factor-1
• Statins
• RANK-L Denosumab

• Antiresorptives
• Estrogens
• Selective estrogen receptor modulators
• Bisphosphonates
• Calcitonin

Others Calcium Vitamin D
35
Bisphosphonates

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

36
Bisphophonates Block Bone Resorption
Inhibits osteoclasts. Binds
to bone
37
Bisphosphonates

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

38
Unusual Complicationsof Bisphosphonates

• Osteonecrosis of jaw-
• Rare 1/100000 patient years
• 94 in cancer patients receiving zoledronic acid
  or pamidronate
• Woo S-B et al. 2006 Ann Int Med 144(10)753-61
• Unusual Fx in some patients with nl BMD
• Neviaser AS et al. 2008 Journal of Orthopaedic
  Trauma 22(5) 346-350
• Lenart et al. 2008 NJEM 358 (12) 1304

39
(No Transcript)
40
Estrogen

• ERT increases BMD and reduced bone markers more
  than 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 (but not recommended as first-line
  therapy)

41
Selective Estrogen Receptor Blocker (SERM)

• Raloxifene (Evista) preferentially binds to the
  alpha estrogen receptor
• fewer estrogen breast cancers
• fewer vertebral fractures
• more venous thromboembolism
• more fatal stroke
• No difference in coronary deaths
• No difference in hip fractures
• RUTH trial Barrett-Connor et al. 2006 NEJM
  355(2)125-37

42
Calcitonin

• Calcitonin is effective for osteoporosis fracture
  pain. Effect takes about 2 weeks.
• Silverman SL. Osteoporos Int. Nov
  200213(11)858-867.
• No significant effect in the hip
• Cost
• Miacalcin 112
• Fortical 54

43
Parathyroid Hormone (PTH)

• Forteo (Teriparatide)
• Daily 20mg or 0.08ml SQ injection
• PTH draws Ca out of cortical bone
• Hip 50 cortical bone
• Spine 10 cortical bone
• Intermittent antiresorptive effect
• Preferential osteoblastgtosteoclast activity
• Weak evidence for hip Fx
• ACP Practice Guideline. Ann Int Med
  2008149404-415

44
Parathyroid Hormone (PTH)

• Forteo (Teriparatide)
• Approved for use of lt2 years
• Neer RM et al. NEJM 2001344(19)1434-41
• Do not use in combination with bisphosphoonate-
  Black et. al. N Engl J Med 2003349(13)1207-15
• Increases BMD 6
• Not very effective for preventing fractures
• Risk of osteosarcoma in animal trials

45
Denosumab - new kid on the block (Brand name
Prolia)

• Denosumab (formerly AMG-162)
• Monoclonal antibody
• Inhibits bone resorption by blocking
• KB-ligand (RANKL)
• Bekker et al. 2004 J Bone Miner Res 191059-66
• Injected twice yearly
• Expensive 1650 per year
• Effect on immune system

46
Summary of Medications

• Bisphosphonates- First line therapy
• Boniva no hip benefit
• Must have GFR gt 30
• Calcitonin only for spine good for pain
• Estrogen good for osteoporosis
• SERM need long term data only spine
• PTH lt2 yrs not in combination
• Denosumab monoclonal antibody 2x/yr

47
Balloon Kyphoplasty

• Stabilizes the Fracture and Corrects Spinal
  Deformity caused by one or more VCFs

Indicated for vertebral compression fracture if
pain not controlled with meds
48
Conclusion

• Osteoporosis is a growing epidemic
• Save yourselves! Preach prevention!
• Test all women over 65 and others at risk for
  osteoporosis (DEXA)
• Treat all elderly and patients at risk with
  Calcium and Vitamin D
• Dont be afraid of bisphosphonates

49
Case 1 - Lilly

• 52 year old Caucasian Female
• Hot flashes
• No hx fx no height loss
• Average height and weight
• No FHx of osteoporosis
• T-score -1.8 at LS -1.5 fem neck

50
Case 1 Lilly (cont)

• What is Lillys diagnosis
• What should we do for sure
• What could we do for good measure

51
Case 1 Lilly (cont)

• Lilly has low BMD (old term osteopenia)
• Calcium and Vit D
• Exercise
• Tx can reduce bone loss but not fracture NNT
  2000
• ERT (0.625mg) can use for hot flashes. Or use
  low-dose i.e. 0.3mg (be sure to add progesterone
  if uterus intact)

52
Case 2 Ms. Greer

• Mrs. Greer is a 68 yo AAF on HRT since menopause.
  
• Wants to stop HRT d/t WHI study.
• Does not take Ca or Vit D.
• Lost 2 inches in height. Fx forearm 2 yrs ago.
• T-score spine -2.0 hip -2.2

53
Case 2 Ms. Greer (cont.)

• What labs should we get
• How should we treat her bones
• When should we recheck her BMD

54
Case 2 Ms. Greer (cont.)

• Labs TSH 25-hydroxyvitamin D PTH 24-h urinary
  calcium were normal
• Start calcium 1200mg Vit D 800 IU
• Bisphosphonate Alendronate 70 mg once a week.
• Recheck BMD in 2 years

55
Case 3 Mrs. Pickens

• 80 yo frail community-dwelling CF lives alone
• No hx fx but has fallen 3 x in 1 yr
• Takes 1000mg Ca in AMs plus MVI
• Stays out of the sun d/t fear of skin Ca and
  wrinkles
• Walks very little d/t fear of falling
• T-score -2.8 at hip -2.0 at spine
• GERD controlled on PPI
• HTN controlled on beta blocker
• What shall we do for Mrs. Pickens

56
Mrs. Pickens (cont.)

• Falls risk assessment
• Meds (hypotension)
• Home assessment
• Strength training exercises
• Eval for secondary causes of osteoporosis
• Vit D 8
• How will you treat her Vit D

57
Mrs. Pickens (cont.)

• Anti-osteoporosis medications
• Which med(s) would you chose
• Bisphoshphonates
• PTH
• HRT
• Raloxifene
• Hip protectors

58
Mrs. Pickens (cont.)

• 10/yr hip fx risk so focus on meds that reduce
  hip fx
• Bisphoshphonates OK if GERD controlled and GFR
  gt 30 (Reclast if esophagus problem)
• PTH second best choice - daily SQ injection
• Denosumab (Plolia) candidate
• HRT risky for CV EM
• Raloxifene not shown to reduce hip fx (only
  vertebral) Increased risk of DVT stop it for
  periods of inactivity.

59
Mrs. Pickens (cont.)

• Vit D 50000 IU ergocalciferol per week for 12
  weeks
• Risondronate 35mg once a week
• Physical Therapy
• Hip protectors

60
Hip Protectors

• Benefit of hip protectors on fracture when worn
• Rubenstein L. NEJM 2000 343(21)1562-3
• No benefit of hip protectors intention to treat
  analysis
• Cummings P and Weiss NS. JAMA 2003 290(7)884
• No benefit with 80 adherence
• Kiel DP et al. JAMA 2007 298(4)413-22
• Cochrane review of 11 studies Marginally
  statistically significant reduction in hip
  fractures
• Parker MJ et al. BMJ 2006332(7541)571-4