1. 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

2. Case Presentation 68 year old female –Mrs. KY
CXR for cough: ‘osteopenic’ bones

3. Outline Management Plan
What further history
Clinical examination
Investigations
Treatment & Prevention

4. History: Mrs. KY Hx of Prior Fractures Falls Hx Neurological D-Z Hx
Hx of Muscular Weakness
Nutritional Hx
Medication Hx
Functional Hx 4

5. Nutritional History: Mrs. KY
Deficiency States
Calcium
Vitamin D
Vitamin C
Excess Intake
Caffeine
Alcohol
Smoking

6. Physical Examination: Mrs. KY
Orthostatics
Gait & Mobility
Height
Kyphosis
Clinical Features of
Hypercortisolism
Hyperthyroid

7. 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
Complete blood count
Multiple myeloma

8. 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

9. Hip
BMD
Spine

10. WHO Definitions Normal T score > -1 SD Osteopenia
Osteoporosis
T score  -2.5 SD
Established Osteoporosis
T score  -2.5 SD + low energy fracture

11. Bone Health Normal Osteoporotic Bone quality is not the only factor …
07/16/13 19:23
Bone Health
Normal
Osteoporotic
Bone quality is not the only factor … 11

12. Diagnosis of Osteoporosis
History: etiology and RFs
Exam: kyphosis, prox weakness
X-rays: fractures
BMD: bone mass
Laboratory tests: etiology, BTOM

13. 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

14. The Domino Fracture Effect
This ‘domino fracture effect’ can lead to impaired mobility and have devastating consequences on a patient’s quality of life through a decline of independence and dignity 14 14

15. Fracture Risk Reduction
Look for risk factors other than low bone mineral density
Minimize over-zealous Rx of those at indeterminate risk

16. 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: 16 16

17. FRAX™. Available at: http://www.shef.ac.uk/FRAX/index.htm.
Prof. John A Kanis University of Sheffield
FRAX™. Available at:

20. Risk factors
The “red flags” for osteoporosis risk. 20

21. Older than 65 # after age 50 Underweight Previous falls FMH of Osteo/#
IDENTIFY RISK FACTORS OF OSTEOPOROSIS 1
Older than 65
# after age 50
Underweight
Previous falls
FMH of Osteo/#

22. > 2 drinks of alcohol/week
IDENTIFY RISK FACTORS OF OSTEOPOROSIS 2
Smoking
> 2 drinks of alcohol/week

23. 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

24. RISK FACTORS OF OSTEOPOROSIS: MEDICATIONS4
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

25. The good news: Osteoporosis is preventable for most people!
Diet and lifestyle

27. Management of Osteoporosis
Treatment / 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
Although the management of Osteoporosis can be broken down into treatment and prevention,in clinical practice the distinction is less appropriate as there is a great deal of overlap and both involve
changes in lifestyle centred around exercise, stopping smoking and diet,
drug therapy to reduce fracture risk
non-pharmacological therapies to reduce the effects of fractures and prevent further fractures.
stopping smoking
Prevention of Falls 27

28. Lifestyle Advice Diet Exercise Smoking Sunlight Exposure Alcohol
Balanced diet containing adequate calcium
1000 mg/day
Exercise
Regular weight bearing exercise 3 times a week for 20 minutes minimum
Smoking
Stop smoking
All patients should receive lifestyle advice re Diet rich in calcium
Alcohol intake
Exposure to sunlight
Stopping smoking
Exercise
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 28

29. Calcium Rich Diet
Vitamin D
Prevent Falls
Weight-Bearing Exercise

30. 30

31. Walking Dancing Gardening Tennis Jump Rope Volleyball Skating
Activity – Exercise Guide

32. Don’t Smoke
Minimize Caffeine & Alcohol
Testing & Medication if Needed

33. Calcium Requirements: age related
Goal
500 mg
1,300 mg

34. Dietary sources of calcium
07/16/13 19:23
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 = mg
= 4.5 glasses of milk 34

36. Vitamin D for Ca absorption
400 IU daily
Vitamin D is in milk (100 IU in 1 cup)

38. Current treatments in OP
Antiresorptive
Estrogens and SERMs
Calcitonin
Bisphosphonates
Denosumab
Anabolic (stimulate bone formation)
Parathyroid hormone
Dual action agents
Strontium ranelate

39. Estrogen WHI raised concerns about CV risks
ERT increases BMD > SERM
Prestwood, KM et al. J Clin Enodocrinol Metab. 2000; 85(6):
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
MORE trial 7705 women mean age 66. 39

40. 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)

41. 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

42. 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

43. Calcitonin Calcitonin is effective for OP fracture pain
Effect takes about 2 weeks.
Silverman, SL. Osteoporos Int. Nov 2002;13(11):
No significant effect in the hip

44. Bisphosphonates Binds to bone Inhibits osteoclast activity
Supports osteoblast bone formation
First line treatment for osteoporosis

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

46. 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 Ann Int Med 144(10):753-61

47. Atypical # 5/10,000; risk: > 5 yrs Rx
NEJM 364;18 nejm.1730 org may 5, 2011

48. 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
Protelos is indicated for patients with postmenopausal osteoporosis:
As a first line alternative to bisphosphonate therapy, particuarly in the elderly
In those with a history or potential for upper gastrointestinal complications
In women who have tried/failed (intolerance or inadequate response) treatment with other osteoporosis therapies.
MHRA Drug Safety Update 2013; 6(9). 48

49. 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

50. 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

51. Convenience/ patient choice
PROLIA®: REAL WORLD
Factors influencing treatment
Efficacy
Adherence
Cost
Convenience/ patient choice
Safety/ tolerability

52. Osteoporosis Prevention and Treatment
Hormonal Replacement
SERM
Treatment
choice
Bisphosphonates
Strontium
PTH
Vitamin D
Life Style 20 40 60 80
Age 52

53. 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

54. 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

55. Calcium/Vitamin D Controversies
Ca/Vit D tablets –harm/benefit

56. Background 36, 282 postmenopausal WHI
1 G Ca IU VitD or Placebo for 7 years
Baseline: 20,000 on personal Ca
Baseline: 16,000 no Ca
Bolland MJ et al. BMJ ;342:d2040

57. RESULTS
NO Personal Calcium Use
ANY Personal Calcium Use
Event
CaD
N=8429
Placebo N=8289
HR 95% CI P HR
95% CI MI
209
168
1.2
(1-1.5)
0.05
180
196
0.92
( )
0.44
CVA
163
( )
0.14
156
189
0.8
(0.7-1)
0.08
MI/ CVA
386
326
1.16
(1-1.4)
324
370
0.9
(0.76-1)
0.09
Bolland MJ et al. BMJ ;342:d2040

58. Bolland MJ et al. BMJ ;342:d2040. 58

59. Bolland MJ et al. BMJ ;342:d2040.

60. Incidence of MI/CVA in Subjects on Calcium
Bolland MJ et al. BMJ ;342:d2040.

61. Ca-VitD Incidence of Death
Bolland MJ et al. BMJ. 2010;341:c3691.

62. 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

63. Calcium: Risk of Death Men vs Women
Xiao Q et al. JAMA Intern Med. 2013;173(8):

64. Calcium: Risk of Death Men vs Women
Xiao Q et al. JAMA Intern Med. 2013;173(8):639-46

65. Implication for Clinical Practice
Recommendation for widespread use of Ca Rx no longer appropriate
Calcium/vitamin D-rich diet favoured
Further studies needed

66. Bone Health Building Blocks

67. 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

68. Thank You