1. Everything a Pharmacist Needs to Know About Osteoporosis
New Mexico Pharmacists Association
Mid-Winter Meeting
January 27-28, 2018
Albuquerque, NM
E. Michael Lewiecki, MD, FACP, FACE
Director, New Mexico Clinical Research & Osteoporosis Center
Director, Bone Health TeleECHO
University of New Mexico Health Sciences Center
Albuquerque, NM

2. Disclosure
Consulting
Amgen, Radius
Speaking
Radius

3. Objectives Recognize osteoporosis treatment guidelines
Define balance of benefits and risk with treatment
Demonstrate risk communication techniques

4. Osteoporosis
A skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture
Bone strength reflects the integration of two main features: bone density and bone quality
NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy March 27-29, Published in JAMA. 2001;285: Images by David Dempster, PhD.

5. Major Public Health Concern
54 million Americans with osteoporosis or low BMD
2 million osteoporotic fractures each year
Direct healthcare costs about $19 billion per year
Increase is mortality, disability, loss of independence
US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Office of the Surgeon General; National Osteoporosis Foundation. Accessed

6. Fracture Risk Assessment Will I end up like my mother?
Intervention Thresholds
Treatment
Follow-up

7. WHO Classification of BMD
T-score
Normal
-1.0 or higher
Osteopenia
Between -1.0 and -2.5
Osteoporosis
-2.5 or lower
Severe Osteoporosis
-2.5 or lower + fragility fracture
Applies to postmenopausal women and men age 50 and older Cannot be used in premenopausal women and men under age Should never be used in children (under age 20) T-score ≤ -2.5 is not always osteoporosis A patient may have osteoporosis with a T-score > -2.5.
WHO Study Group ISCD Official Positions.

8. NOF Treatment Guidelines
For postmenopausal women and men age 50 and older, after appropriate evaluation for secondary causes
Osteoporosis by T-score
T-score -2.5 or less at FN, TH, or LS, or . . .
Clinical Osteoporosis
Hip or vertebral (clinical or morphometric) fracture, or . . .
Low BMD + High Fx Risk
T-score between -1.0 and -2.5 at FN, TH, or LS, and . . .
FRAX 10-year probability of hip fracture ≥ 3% or major osteoporotic fracture ≥ 20%
National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis

9. Medications for Osteoporosis
Inhibit Bone Resorption
(Antiresorptive)
Stimulate Bone Formation
(Anabolic)
Alendronate (Fosamax, generic)
Teriparatide (Forteo)
Risedronate (Actonel, Atelvia, generic)
Abaloparatide (Tymlos)
Ibandronate (Boniva, generic)
Zoledronate (Reclast, generic)
Denosumab (Prolia)
Raloxifene (Evista, generic)
Salmon Calcitonin (Miacalcin, generic)
Estrogen (various)
CE/Baxedoxifene (Duavee)

10. Individualizing Initial Treatment
Agent
Comments
Oral BPs
Pro: inexpensive, work well in many patients
Con: GI distress, avoid with low GFR, bad rep in lay press
ZOL
Pro: very long dosing interval, post-hip fracture data
Con: acute phase reaction, avoid with low GFR, IV
Dmab
Pro: long dosing interval, greatest BMD increase, SC
Con: FDA list of “side effects” (back pain, high cholesterol, etc.)
TPT
Pro: anabolic
Con: high cost, daily injection, refrigeration, rat osteosarcoma
Abalo
Pro: anabolic, no refrigeration, less hypercalcemia than TPT
Con: cost, daily injection, rat osteosarcoma
RLX
Pro: not a BP, decreases breast cancer risk
Con: VTE, hot flashes, no proven hip fracture decrease
Personal opinion.

11. Indications  Medication PMO GIO (Women, Men) Men Prevention Treatment
Estrogen (many forms) 
CE/BZA (Duavee)
Raloxifene (Evista, generic)
Alendronate (Fosamax, generic)
Risedronate (Actonel, generic)
Risedronate DR (Atelvia)
Ibandronate PO (Boniva, generic)
Ibandronate IV (Boniva)
Zoledronate (Reclast, generic)
Calcitonin IN (Miacalcin, generic)
Denosumab (Prolia)
Teriparatide (Forteo)
Abalopartide (Tymlos)
Paget’s dose: Fosamax 40 mg/day x 6 mo., Actonel 30 mg/day x 2 mo.
Launch Dates: Fosamax 10/95, Miacalcin 1/96, Evista 1/98, Actonel 5/00, Weekly Fosamax 11/00

12. Fracture Risk Reduction in RCTs
Medication
Spine
Nonvertebral
Hip
Estrogen (many forms) 
CEE/BZA (Duavee)
/ 
/-
Raloxifene (Evista, generic)) -
Alendronate (Fosamax, generic)
Risedronate (Actonel, generic)
Ibandronate (Boniva, generic)
( in post hoc analyses)
Zoledronate (Reclast, generic)
Calcitonin (Miacalcin, generic)
Denosumab (Prolia)
Teriparatide (Forteo)
Abaloparatide (Tymlos)

13. A Brief History of Osteoporosis How did we get where we are today?
E. Michael Lewiecki, MD
Personal Opinion

14. Osteoporosis Care CRISIS Better Worse Then Now
USA DXA Reimbursement Cuts (2007)
WHI (2002)
ONJ
AFF
Bureaucracy
Media Reports
FRAX
Limited Time
Fear of Side Effects
Guidelines
Competing Priorities
More Marketing
Drug Holidays
Approval of More Drugs
Calcium
Competing Guidelines
US Surgeon General’s Report
Vitamin D
Increasing Availability of DXA
Risk Communication
Bone Mass Measurement Act
Treatment Gap
Mass Marketing
CRISIS
Approval of Alendronate (1995)
WHO Diagnostic Criteria (1994)
DXA Introduced (1987)

15. Treatment Gap Getting Worse
Review of US insurance claims data (commercial + Medicare)
in 96,887 patients hospitalized with hip fracture,
Solomon DH et al. J Bone Miner Res. 2014;29:1929–1937.

16. Reduced Bisphosphonate Prescription Rates Starting in 2008
Jha S et al. J Bone Miner Res. 2015;30:

17. US Hip Fracture Trends 2002-2015
Hip Fracture Rates
DXA Medicare Payments
$139
Osteoporosis Diagnosis
$82
$42
DXA Testing

18. Strategies to Reduce the Treatment Gap
Public awareness / empowerment of patients
Shared decision making
Alignment of incentives
More effective use of current treatments
New drug development
Harmonization of guidelines
Fracture liaison services
Better risk communication
Restore DXA reimbursement
Improve DXA quality
Treat-to-target
Sharing knowledge (Bone Health TeleECHO)

19. Can pharmacists help?

20. Survey of 1,222 Community Pharmacists in Canada
Screening for Osteoporosis
Screening for Risk of Falls
Believed should be involved
47%
50%
Actually were involved
17%
19%
Barriers to providing these services
Lack of time: 79%
Lack of clinical tools: 65%
Lack of coordination with other healthcare professionals: 55%
Laliberte M-C et al. Osteoporos Int. 2013;24:

21. Systematic Review of Pharmacist Interventions for Osteoporosis Care
25 studies identified (3 RCTs)
Interventions included patient counseling, education, QUS, and physician contact
Results: interventions increased DXA testing and calcium intake in high risk patients
Limitations: study bias, no study examined adherence to treatment, more and better designed studies are needed
Elias MN et al. Osteoporos Int. 2011;22:

22. What You Can Do (If you have the interest, the time, and the resources)
Identify patients who qualify for DXA testing
Educate patients on long-term glucocorticoids on high risk of fracture
Counsel on falls prevention, calcium, and vitamin D
Distribute educational materials
Inform on correct administration of oral BPs
Advise fracture patients on risk of future fractures
Communicate balance of benefits and risks
Assess adherence to therapy
Recognize the myths, understand the data, and appreciate the uncertainties in osteoporosis care

23. Controversies / Uncertainties
Evaluation
Treatment
DXA
Indications
Testing intervals
Quality
Reimbursement
Fracture risk assessment
Wise use of FRAX
Other algorithms
Secondary causes
Best w/u for a patient
Non-pharmacological
Best exercise
Calcium and CV disease
Target vitamin D level
Pharmacological
Initial drug selection
How long to treat
Changing therapy
Combining therapy
Benefit vs. risk

24. Indications for DXA Women age ≥ 65 and men age ≥ 70
Younger postmenopausal women, perimenopausal women, and men age based on risk factor profile
Adults with fragility fracture, disease or condition associated with low BMD or bone loss
Extracted from NOF Clinician’s Guide to Prevention and Treatment of Osteoporosis and ISCD Official Positions, 2015.

25. There is no safe dose of prednisone
High Fracture Risk with Any Dose UK General Practice Research Database 244,235 oral glucocorticoid users compared to 244,235 controls
Prednisone: < 2.5 mg/day
mg/day
≥ 7.5 mg/day
There is no safe dose of prednisone
van Staa TP et al. J Bone Miner Res. 2000;15:

26. From Osteoporosis Canada at http://www.osteoporosis.ca

27. From American Bone Health at https://americanbonehealth.org/

28. From National Osteoporosis Foundation at https://www.nof.org

29. “Calcium with or without vitamin D intake from food or supplements has no relationship (beneficial or harmful) to the risk for cardiovascular and cerebrovascular disease, mortality, or all-cause mortality in generally healthy adults at this time.”
Kopecky SL et al. Ann Intern Med. 2016;165(12):

30. Osteoporosis Wheel of Fear

31. Bisphosphonate Safety Issues
Side Effects
“Side Benefits”
Short-term
GI distress
Acute phase reaction
Hypocalcemia
Renal toxicity
Long-term
Osteonecrosis of the jaw
Atypical femur fractures
Questionable
Chronic musculo-skeletal pain
Atrial fibrillation
Esophageal cancer
Impaired fracture healing
Improved implant survival
 risk of breast cancer
 risk of endometrial cancer
 risk of colorectal cancer
 risk of stroke
 risk of gastric cancer
 risk of MI in RA patients
 risk of type 2 DM
 mortality
Prieto-Alhambra D et al. Arthritis Rheum. 2014;66:
Chlebowski RT et al. J Clin Oncol. 2010;28:
Newcomb PA et al. J Clin Oncol. 2015;33:
Dreyfuss JH. CA Cancer J Clin. 2010;60:
Newcomb PA et al. Br J Cancer. 2010;102:
Rennert G et al. J Clin Oncol. 2010;28:
Vestergaard P et al. Calcif Tissue Int. 2011;88:
Rennert G et al. J Clin Oncol. 2011;9:
Kang JH et al. Osteoporos Int. 2012;23:
Abrahamsen B et al. J Bone Miner Res. 2012;27:
Center JR et al. J Clin Endocrinol Metab. 2011;96:
Wolfe F et al. J Bone Miner Res. 2013;28:
Konstantinos A et al. J Clin Endocrinol Metab. 2015;100:
Sambrook PN et al. Osteoporos Int. 2011;22:
Lee P et al. J Clin Endocrinol Metab. 2016;101:

32. Denosumab Safety
Message to patients: “The most common side effects of Prolia® include back pain, pain in the arms and legs, high cholesterol, muscle pain, and bladder infections.”
Adverse reactions in ≥ 2% of Patients with Osteoporosis
and More Frequent Than with PBO
Term
Prolia (N=3886)
PBO (N=3876)
Back Pain
1347 (34.7%)
1340 (34.6%)
Pain in extremity
453 (11.7%)
430 (11.1%)
Hypercholesterolemia
280 (7.2%)
236 (6.1%)
Myalgia
114 (2.9%)
94 (2.4%)
Cystitis
228 (5.9%)
225 (5.8%)
and package insert May 2017.

33. Osteonecrosis of the Jaw
Ruggiero SL. J Oral Maxillofac Surg. 2004;62:

34. Atypical Femur Fractures
Unadjusted and Age-adjusted Risk of AFF According to Duration of Bisphosphonate Therapy
Years of Bisphosphonate Exposure
Incidence of AFF per ,000 person-years
Atypical Femur Fracture
Risk of AFF increases with duration of BP therapy (1).
Risk of AFF is low in proportion to fractures prevented by BP therapy (1).
After BP withdrawal, risk of AFF rapidly decreases by 70% per year (2).
1. Dell RM et al. J Bone Miner Res. 2012;27:2544–2550; 2. Schilcher J et al. N Engl J Med. 2011;364:

35. 10-Year Probabilities 80 year-old woman with FN T-score = -3.3
Includes 0.01% Atypical Femur Fracture Risk
Includes 0.5% Atypical Femur Fracture Risk
Untreated probability of major osteoporotic fracture calculated by FRAX. ONJ estimate is ~1/100,000 patient-treatment-years from ASBMR Task Force by Khosla S et al. J Bone Miner Res 2007;22:1479–149. AFF estimate untreated is ~0.01/10,000 and treated is ~5/10,000 patient-years from Schilcher J et al. N Engl J Med. 2011;364: Risk estimates assume long-term bisphosphonate therapy resulting in 50% reduction in fracture risk. MVA and murder data from the CDC at Image copyright © 2011 Lewiecki EM. Slide version.

36. Motor Vehicle Accidents
Benefits and Risks
Motor Vehicle Accidents
Osteoporosis
Wearing seat belts reduces the risk of serious crash-related injuries and deaths by about 50%
Treatment with bisphosphonates reduces the risk of fractures by about 50%
There are about 2.3 million adults treated in ERs each year for injuries from MVAs and about 2 million osteoporotic fractures each year. The risk of seat belt injuries and serious side effects from osteoporosis treatment is very small in proportion to the benefits. Data from multiple sources.

37. Myth: Osteoporosis Drugs Don’t Work After 5 Years
Reality: The evidence supports anti-fracture efficacy for as long as 10 years in appropriately selected patients
Uncertainty
RCTs with a placebo group are typically 3 years for osteoporosis drugs
No data beyond 10 years
Studies with other drugs for chronic diseases are often far shorter, and we typically don’t know the long-term effects of any drugs for any disease

38. Drug Holiday
Elective temporary withholding of bisphosphonate after at least 3-5 years in appropriate patients
NOT “drug retirement”
NOT “stopping treatment”
NOT for non-bisphosphonates
Rationale: persistence of anti-fracture benefit while possibly reducing long-term risks
Very little data, many opinions
Periodic reevaluation of balance of benefits and risks
Adapted from Whitaker M et al. N Engl J Med. 2012;366: Black DM et al. N Engl J Med. 2012;366: Bonnick SL. J Clin Densitom. 2011;14: Watts NB et al. J Clin Endocrinol Metab. 2010;95:

39. Adler RA et al. J Bone Miner Res. 2016;31:16–35.

40. Postmenopausal Women Treated with Oral BP ≥ 5 Years or IV BP ≥ 3 Years
Low fracture risk: hip T-score > -2.5 and no hip, spine, or multiple osteoporotic fracture before or during therapy
Consider drug holiday of 2-3 years
High fracture risk: hip T-score ≤ -2.5 or hip, spine, or multiple osteoporotic fracture before or during therapy
Consider continuing oral BP up to 10 years and IV BP up to 6 years
Adler RA et al. J Bone Miner Res. 2016;31:16–35.

41. No Holiday with Denosumab

42. Loss of Fracture Protection after Discontinuation of Denosumab
Systematic review of literature on discontinuing Dmab
Return of fracture risk to baseline after discontinuation and possible increase in risk of multiple VFs
Stopping Dmab should be followed by alternative treatment
Tsourdi E et al. ECTS Position Statement. Bone Epub.

43. Sequencing with Anabolic Therapy
Anabolic after potent BP (ALN) - delay or attenuation of anabolic effect
Anabolic after Dmab - BMD decrease transient/sustained
Anabolic after mild antiresorptive (ET, RIS) - expected onset of anabolic effect
Antiresorptive after anabolic - essential

44. Bone Health

45. USA Participants: 21 Months
Bone Health
USA Participants: 21 Months
263 registered, 221 attended at least once, attendees each week
Other countries
Canada
Mexico
Chile
Brazil
Trinidad and Tobago
Ireland UK
Lewiecki EM et al. ASBMR

46. Self-Efficacy Outcomes Measures
Bone Health
Self-Efficacy Outcomes Measures
Bone Health ECHO learners with direct patient care responsibilities who attended more than 10 clinics (n=10)
Expert
Very competent
Competent
Average
Slight skills
Vague skills
No skills
N/A
After ECHO*
Before ECHO
Lewiecki EM et al. ASBMR
*P = (very large effect size; Cohen and Sawilowsky)

47. Summary
Osteoporosis is a common disease with serious consequences due to fractures
Despite availability of effective and safe medications to reduce fracture risk, there is a large treatment gap
We can do better