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Osteoporosis

Learning objectives :
Burden of the disease. Screening and treatment guidelines. Bisphosphonates. Controversial topics : Association of bisphosphonates with

ONJ Atypical femoral fractures Atrial fibrillation. Esophageal cancer.

Burden of Disease
million people in US have Osteoporosis

10
33

million people in US have

Osteopenia.

Burden of Disease

fractures/year due to either.


300,000 HIP fractures.

> 2 million

547,000 vertebral fractures. 135,000 pelvic factures.

Burden of Disease :

Hip fractures
mobility.

50 % 25 %

Permanent impaired

Loose skills to live

independently. Increased all cause mortality : first 3 months after hip fracture.
1.2010 position statement of the North American Menopause Society. Menopause 2010.

Annual incidence

Osteoporosis

Risk factors

Who to screen

Women > 65 years. Men > 70 years. Postmenopausal women /men >50 years with clinical risk factors. H/o fracture at age > 50 years. Chronic steroid use.

Who to treat ?
Postmenopausal women /men > 50 yrs

with
Prior h/o hip/vertebral #

or
T Score < -2.5

or
T Score -1 to -2.5 & 10 yr risk (FRAX) : HIP # > 3 % or major osteoporotic # > 20 %

Calcium and vitamin D

Mainstay of treatment :
Bisphosphonates
Approval in US for osteoporosis Alendronate : 1995 Risedronate : 2000 Ibandronate : 2005 Zoledronate : 2007.

Therapeutic strategies
Stimulators of Bone Formation
Fluoride PTH analogs Sr Ranelate (?)

Bone marrow precursors

Inhibitors of Bone Resorption


Estrogen, SERMs Bisphosphonates Calcitonin

Inhibitors of RANKL Cathepsin K Osteoclast Osteoblasts Lining cells

Clinical Evidence

THE LANCET Vol 348 December 7, 1996

Taking Bisphosphonates

Contraindications

Duration of treatment

Cost factor

Alendronate: $4 $40/month Risedronate : $60 $120/month Ibandronate (oral): $90 - $130/month IV Ibandronate : $1300/year IV Zoledronate : $1300/year

Hot topics

Osteonecrosis of jaw

ONJ
Osteoporosis :

Reporting rate 1/100,000 - 1/250.000. True incidence may be higher.

Malignancy/skeletal metastasis :

Estd. Incidence: btw 1- 10 %

Risk factors

Recommendations

Atypical fractures

Atypical fractures

? Long term over suppression of bone turnover. Incidence : 1 in 10,000. Associated median treatment duration : 7 years. Causality : long term bp/ atypical # unproven. Further large scale studies needed.

Recommendations

Educate physician/patient about Prodromal pain. Evaluate with urgent X-Ray. If negative, may consider MRI. Stop BPs if atypical fracture confirmed.

Atrial fibrillation

FDA recommends physicians to not alter their prescribing patterns while it continues to monitor post marketing reports of AF in such patients. In v/o above and absence of definitive data : Benefits of treatment outweigh risks.

Esophageal cancer

23 cases reported in last 2 decades. (Wysowski et al) 31 cases from Europe/Japan. Median time from use to diagnosis : 1-2 yr. Time from exposure inconsistent w/ causal relation. Further studies needed.

Renal safety

Safe for creatinine clearance > 30 -35 ml/min. Lack of experience < 30 ml/min. No data for use in ESRD. Exact bone disease unknown unless biopsy. Expert opinion: half the dose could be used for 3 years in ESRD once bone biopsy confirms osteoporosis.

Take home points

Osteoporosis : significant burden of disease. Main stay treatment : bisphosphonates. ? Duration of treatment : individualized. More research needed to confirm association with ONJ, Subtrochanteric fracture. Benefits of treatment outweigh risks in osteoporosis.