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Osteoporosis

BONE LOSS
Since you can't see or feel bone loss, it can happen without you knowing, increasing your risk of fracture. After menopause, taking calcium supplements is important, but alone may not be enough to prevent fractures caused by osteoporosis.

Bone resorption exceeds bone formation

Cancellous bone
cancellous bone, also called trabecular bone or spongy bone, light, porous bone enclosing numerous large spaces that give a honeycombed or spongy appearance. The bone matrix, or framework, is organized into a three-dimensional latticework of bony processes, called trabeculae, arranged along lines of stress. The spaces between are often filled with marrow

Compact Bone
compact bone, also called cortical bone, dense bone in which the bony matrix is solidly filled with organic ground substance and inorganic salts, leaving only tiny spaces (lacunae) that contain the osteocytes, or bone cells. Compact bone makes up 80 percent of the human skeleton; the remainder is cancellous bone, which has a spongelike appearance with numerous large spaces and is found in the marrow space (medullary cavity) of a bone. Both types are found in most bones. Compact bone forms a shell around cancellous bone and is the primary component of the long bones of the arm and leg

Osteocytes, osteoblasts
Osteoblasts are mononucleate cells that are responsible for bone formation. osteoblasts are specialized fibroblasts. Osteoblasts produce a matrix of osteoid, which is composed mainly of Type I collagen. Osteoblasts are also responsible for mineralization of this matrix. Bone is a dynamic tissue that is constantly being reshaped by osteoblasts, in charge of production of matrix and mineral, and osteoclasts, which remodel the tissue. Osteoblast cells tend to decrease with age, affecting the balance of formation and resorption in the bone tissue

Fibroblasts
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen,[1] the structural framework (stroma) for animal tissues, and plays a critical role in wound healing

Osteoclasts
An osteoclast is a type of bone cell that removes bone tissue by removing its mineralized matrix and breaking up the organic bone (organic dry weight is 90% collagen). This process is known as bone resorption.

Osteoporosis

Normal Bone

Osteoporotic Bone

Normal Bone

Moderate Osteoporosis

Severe Osteoporosis

Courtesy of Dr. A. Boyde

OSFIT

OSFIT

OSFIT

Will I end up like my mother?

But, do I really have to take those medicines?

Fracture Risk Assessment

Intervention Thresholds I saw on the News last night.....

Treatment

Follow-up

Leading the Effort to Help Prevent and Treat Osteoporosis


Surgeon Generals Report on Bone Health and Osteoporosis

Pharmacotherapy
(antiresorptives and anabolics)

Address Secondary Factors


(drugs and diseases)

Lifestyle Changes Pyramid for Osteoporosis Prevention and Treatment (nutrition, physical activity, and fall prevention)

What does this mean for your patients?


US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. US Department of Health and Human Services, Office of the Surgeon General; 2004.

Fractures in Women Are Common: Incidence of Chronic Diseases


2.0

Annual Incidence, million

1,500,000
1.5

1.0

0.5

250,000

345,000

373,000 211,240 Stroke2


All women

Fracture1

Hip fracture1

Heart attack2

Breast cancer3

Women with osteoporosis

Risk of osteoporotic fracture in 1 year is greater than combined risk of heart attack, stroke, and breast cancer.
1. Riggs BL, Melton LJ III. Bone. 1995;17(suppl):505S511S. 2. American Stroke Association. Heart disease and stroke statistics2005 update. Available at: http://www.americanheart.org. Accessed August 24, 2005. 3. American Cancer Society. Cancer facts & figures; 2005. Available at: http://www.cancer.org. Accessed August 24, 2005.

Osteoporosis
Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. NIH Consensus Development Conference, March 2000

Normal Bone

Osteoporotic Bone

Practical Definition of Osteoporosis

A fall from a sitting or standing height that causes a fracture

Bone Mineral Density Testing


Quantitating the Bone Mass

Central Devices

GE Lunar Prodigy Hologic Delphi

Central DXA
Measures bone density at the hip and spine

DXA image of the hip

DXA image of the lumbar spine

NOF 2008 Guidelines


Who Should be Tested?

Women age 65 and older Men age 70 and older Women and men over 50 with risk factors Patients with a fracture after age 50

Leading the Effort to Help Prevent and Treat Osteoporosis


Surgeon Generals Report on Bone Health and Osteoporosis
Pharmacotherapy
(antiresorptives and anabolics)

Address Secondary Factors


(drugs and diseases)

Lifestyle Changes Pyramid for Osteoporosis Prevention and Treatment (nutrition, physical activity, and fall prevention)

What does this mean for your patients?


US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. US Department of Health and Human Services, Office of the Surgeon General; 2004.

Lifestyle Issues
Tobacco- eliminate it Alcohol moderate it Food eat it Exercise do it Fall Prevention work on it

Lifestyle Issues
Tobacco - eliminate it Alcohol moderate it Nutrition - adequate weight, protein-magnesium, trace elements....multivite Exercise strength, aerobic, flexibility, balance Fall prevention- home safety, shoes, walking aids, glasses

Nutrition
Appropriate Body Weight
BMI 22 - 25

Adequate nutrition
Protein

Multi-vitamin daily
C, D, K, Copper, Manganese, Zinc, Phosphorus

Nutritional supplements
Ensure, Boost

Nutrition
Milk, Yogurt
Calcium, magnesium, potassium, phosphorus, zinc, protein, vitamin A, vitamin D, vitamin B12, riboflavin
Risk reduction for
Osteoporosis, hypertension, obesity, colon cancer, diabetes, metabolic syndrome

Exercise
Walking reduces hip fracture risk
4 hours per week reduced hip fracture by 41% in a study of 61,200 women
JAMA 2002

Activity of any type reduces fracture riskBalance, Strength, Flexibility

Falling
Medications, Alcohol Balance programs Strength training Safety at home Hip protectors Walking aids

Vitamin D 800-2000 IU ?
Vitamin D is important for good bone health because it aids in the absorption and utilization of calcium. There is a high prevalence of Vitamin D deficiency in nursing home residents, hospitalized patients, and adults with hip fractures. ..and many others
Surgeon Generals Report on Bone Health 2004

Vitamin D
Sufficiency > 32 ng/ml Comfort zone- 40s, 50s
Many wellness relationships

Insufficiency < 32 ng/ml


Disease states
New England Journal of Medicine July 19 2007 Medical Progress: Vitamin D Deficiency M F Holick

800-1000 IU daily for patients 50 +


...although some elderly patients may require 2000 IU/day......

NOF Clinicians Guide 2008

Vitamin D
Improves calcium absorption Direct action on building bone matrix Decreases FALLS Increases muscle mass and strength Etc etc................

Leading the Effort to Help Prevent and Treat Osteoporosis


Surgeon Generals Report on Bone Health and Osteoporosis
Pharmacotherapy
(antiresorptives and anabolics)

Address Secondary Factors


(drugs and diseases)

Lifestyle Changes Pyramid for Osteoporosis Prevention and Treatment (nutrition, physical activity, and fall prevention)

What does this mean for your patients?


US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. US Department of Health and Human Services, Office of the Surgeon General; 2004.

Frailty Factor
Acute Medical Illnesses Chronic Medical Illnesses

Sarcopenia
(degenerative loss of skeletal muscle mass and strength associated with aging)

Falling

Medication Check
Corticosteroids Anticonvulsants PPIs SSRIs

Narcotics Cancer Chemo Lithium Thiazolidinediones

Leading the Effort to Help Prevent and Treat Osteoporosis


Surgeon Generals Report on Bone Health and Osteoporosis
Pharmacotherapy
(antiresorptives and anabolics)

Address Secondary Factors


(drugs and diseases)

Lifestyle Changes Pyramid for Osteoporosis Prevention and Treatment (nutrition, physical activity, and fall prevention)

What does this mean for your patients?


US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. US Department of Health and Human Services, Office of the Surgeon General; 2004.

Pharmacotherapy

(Medications)

Medications
Prevent and Treat Thresholds
1. The Fracture Patient or < or = -2.5 T score 2. Bone density = or < - 2.0 3. Bone density = or < -1.5 with risk factors Guidelines for post menopausal women And men over 50

2008 NOF Clinicians Guide


&

FRAX
www.nof.org/professionals/Clinicians_Guide.htm

http://www.shef.ac.uk/FRAX
NOF - National Osteoporosis Foundation FRAX - WHO Fracture Risk Assessment Tool

NOF 2008 Guidelines


Who Should Be Treated?

Fragility fracture- hip or spine T-score -2.5 T-score -1.0 to -2.5 (osteopenia) and
10-year all major osteoporosis-related fracture probability of 20% or a 10-year hip fracture probability 3% (FRAX)

www.nof.org

Leading the Effort to Help Prevent and Treat Osteoporosis


Surgeon Generals Report on Bone Health and Osteoporosis

Pharmacotherapy
(antiresorptives and anabolics)

Address Secondary Factors


(drugs and diseases)

Lifestyle Changes
(nutrition, physical activity, and fall prevention)

Pyramid for Osteoporosis Prevention and Treatment

What does this mean for your patients?


US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. US Department of Health and Human Services, Office of the Surgeon General; 2004.

Anti-Resorptives (Anti-Catabolics)

Bisphosphonates
Estrogens (HRT) SERMs
Raloxifene

Calcitonin

SERMs - Selective Estrogen Receptor Modulators

NOF 2008 Treatment Guidelines


Postmenopausal women and men age 50 and older with the following should be considered for treatment, after evaluation for secondary causes of osteoporosis:

Osteoporosis T-score -2.5 or less at FN or LS after evaluation for secondary causes, or Hip or vertebral (clinical or morphometric) fracture

Osteopenia T-score between -1.0 and -2.5 at FN or LS, and FRAX 10-year probability of major osteoporotic fracture 20% or hip fracture 3%

National Osteoporosis Foundation. Clinicians Guide to Prevention and Treatment of Osteoporosis. 2008.

Osteoporosis:
A disease characterized by low bone mass and deterioration of bone structure that causes bone fragility and increases the risk of fracture1

1US

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; 2004.

The Cells of bone


Osteocytes (osteo-,bone + cyte, cell) Mature bone cells Most abundant

Osteoblasts (OS-te-o-blasts; blast,precursor) Produce new bone matrix


Osteoclasts (os-te-o-clast; clast, to break) Remove & recycle bone matrix

The Matrix of Bone


Calcium phosphate, Ca3 (PO4) +

Calcium hydroxide, Ca(OH)2


= Hydroxyapatite (crystals), Ca10(PO4)6(OH)2

Adherence in the Osteoporosis Patient

54

Medication-Taking Behaviors
Most common types of non-adherence

Not having prescription filled Taking incorrect dose Taking dose at the wrong time Forgetting one or more doses Stopping medication too soon

Always

Never

Sometimes

Patients who are nonadherent visit physicians 3 times as often as comparable patients
American Pharmaceutical Association. Medical compliance, adherence and persistence (CAP) digest. APhA: Washington, DC 2003.

55

BALTO I
BONIVA, ALendronate Trial in Osteoporosis
Patient preference study
Once-monthly dosing of Ibandronate vs Once-weekly dosing of Alendronate

56

BALTO I Study Objectives

Primary objective: - Evaluate patient-reported preference for either once-monthly dosing of Ibandronate (BONIVA) or once-weekly dosing of alendronate Secondary objective: - Assess convenience of once-monthly dosing of Ibandronate (BONIVA) vs once-weekly dosing of alendronate BMD increases and fracture reductions were not assessed

Emkey R, et al. Curr Med Res Opin. 2005;21:1895-1903. 57

BALTO I Patients Preferred Once-Monthly Dosing ofIBandronate (BONIVA)


7.4% (n=22)

BONIVA ALN No preference

26.5% (n=79)

66.1%* (n=197)

Preferred Treatment Dosing Regimen

Most common reasons given for patient preference were: Ease of following a treatment dosing regimen for a long time Dosing regimen fits patients lifestyle better

* p<.0001 Preference expressed 1 treatment dosing regimen over the other (modified ITT) population Emkey R, et al. Curr Med Res Opin. 2005;21:1895-1903.

BALTO I Patients Found Once-Monthly Dosing of Ibandronate (BONIVA) More Convenient

10.8% (n=32)

22.6% (n=67)

66.6%* (n=197)

Preferred Treatment Dosing Regimen

* p<.0001 Preference expressed 1 treatment dosing regimen over the other (modified ITT) population Emkey R, et al. Curr Med Res Opin. 2005;21:1895-1903.

BALTO I Conclusions
A significantly greater percentage of patients preferred once-monthly Ibandronate (BONIVA) dosing to once-weekly alendronate dosing and found the once-monthly regimen to be more convenient Most common reasons given for patient preference were: The ease of following a treatment dosing regimen for a long time Dosing schedule fitting better into the patients lifestyle These results were confirmed in a second replicate study, BALTO II

Emkey R, et al. Curr Med Res Opin. 2005;21:1895-1903. 60

IBANDRONATE SODIUM

A Bisphosphonate

Indications
Ibandronate is indicated for the treatment and prevention of osteoporosis in postmenopausal women In postmenopausal women with osteoporosis, Ibandronate increases BMD and reduces the incidence of vertebral fractures Ibandronate may be considered in postmenopausal women who are at risk of developing osteoporosis and for whom the desired clinical outcome is to maintain bone mass and to reduce the risk of fracture

Bisphosphonates
Adverse events
GI (same as placebo in studies) Flu-like Acute Phase Reaction Bone pain Hypocalcemia Iritis/Uveitis ONJ - Osteonecrosis of the jaw Unusual subtrochanteric fractures

Comparative Risks
Any Fragility Fracture (1) Hip Fracture (1) Anaphylaxis from PCN Shot Death by MVA Death by Murder ONJ- Osteoporosis Patient Death by Lighting Strike in NM
0
(1) Women age 65-69 (from Swedish National Bureau of Statistics and database of Olmsted County, MN, USA.)

2668 387 32 11 6 0.7 0.6


10 20 30 40 50 60 70 80 90 100

Risk per 100,000 People per Year

Kanis JA et al. Osteoporos Int. 2001;12:417-427. Pharmcoepidemiol Drug Saf. 2003;12:195202. National Center for Health Statistics. JADA. 2006;137:1144-1150. www.nssl.noaa.gov/papers/techmemos/NWS-SR-193/techmemo-sr193-4.html

Contraindications
Ibandronate is contraindicated in patients
Who are unable to stand or sit upright for at least 60 minutes With uncorrected hypocalcemia With known hypersensitivity to Ibandronate or any of its excipients

65

Warnings
Ibandronate, like other bisphosphonates

administered orally, may cause upper gastrointestinal disorders such as dysphagia, esophagitis, and esophageal or gastric ulcer Patients should be advised to comply with dosing instructions to minimize the risk of these effects

Precautions
Hypocalcemia and other disturbances of bone and mineral metabolism should be effectively treated before starting therapy Adequate intake of calcium and vitamin D is important in all patients

Ibandronate are not recommended for use in patients with severe


renal impairment (creatinine clearance <30 mL/min) Rarely, patients have reported severe bone, joint, and/or muscle pain after taking bisphosphonates for osteoporosis Additionally, osteonecrosis of the jaw has rarely been reported in patients treated with bisphosphonates; most cases have been in cancer patients undergoing dental procedures

Drug Interactions
Ibandronate do not undergo hepatic metabolism and do not inhibit the hepatic cytochrome P450 system. Products containing calcium and other multivalent cations (such as aluminum, magnesium, iron) are likely to interfere with absorption of Ibandronate. Since aspirin, NSAIDs, and bisphosphonates are all associated with gastrointestinal irritation, caution should be exercised in the concomitant use of aspirin or NSAIDs with Ibandronate.

Conclusions on
Improving Medication Adherence

and Health Outcomes


in Osteoporosis Patients

Conclusions

Adherence to osteoporosis medications is a significant problem only recently getting the attention it needs Poor adherence impacts short- and long-term health outcomes in patients with osteoporosis

Targeted provider interventions may also improve patient adherence in osteoporosis


Strong patient preference for less-frequent-dosing regimens indicates that such dosing regimens may improve adherence in the osteoporosis patient population