Management of osteoporosis finalPresentation Transcript
Systemic skeletal disease.
Low bone mass.
Microarchitectural deterioration of bone tissue.
Increase in bone fragility.
Susceptibility to fracture.
Hip,spine,wrist ,ankle ,humerus
A major health problem.
Consequences include - illness, pain, functional limitations, reduced quality of life, loss of independence, inability to work and even death.
1 out of 3 women (33.3%) &1 out of 8 men (12.5%) suffer from osteoporosis related fracture in lifetime
Grave disease, highly under diagnosed and under treated.
Diagnosis: x-ray -No
Apparent only after 50 -70 % reduction in bone mass
Bone Mineral Density
DEXA :DUAL Energy X-ray Absorptiometry-Gold standard
Single X-ray Absorptiometry /
ULTRASONIC BONE DENSITOMETER
No ionizing radiation
GOLD STANDARD 05/01/10
WHO Classification Normal : BMD within 1 to -1 SD Osteopenia :BMD -1 - 2.5 SD Osteoporosis :BMD -2.5 SD or more 05/01/10
Change of life style most important
Regular exercise must
Stop smoking and alcohol intake
If on steroids / phenytoin taken for long then alendronate must be given
Adequate exposure to sun
CALCIUM AND VITAMIN D
Calcium and Vit D are main stay.
Calcium 1000 mg /day with SERM/Alendronate/HT
1500 mg /day if no therapy
Calcium carbonate does not cause renal calculi
Vitamin D :Dose 400 IU < 70 yrs
700 – 1000 IU > 70 yrs
watch for Hypercalcemia / Hypercalciurea on long term use
No extra benefit for idiopathic postmenopausal osteoporosis
Updated National Osteoporosis Foundation (NOF) guidelines 2008
After introduction of FRAX ® pharmacologic treatment is recommended for postmenopausal women over age 50 with
A hip or vertebral (clinical or morphometric) fracture.
T-score ≤ –2.5 at the femoral neck or spine after appropriate evaluation to exclude secondary causes.
Low bone mass (T-score between –1.0 and –2.5 at the femoral neck or spine) and a 10-year probability of a hip fracture ≥ 3% or a 10-year probability of any major osteoporosis-related fracture ≥ 20% based on US-adapted WHO absolute fracture risk model ( FRAX ® ).
NOF. Clinician’s Guide. 2008;1-36 .
Drugs available and on horizons
Antiresoptives- Inhibit osteoclastic activity
New drugs in pipeline
Anabolic stimulate bone fromation
PREVOS / SOTI / TROPOS
• Women’s Health Initiative (WHI)
– 16,608 postmenopausal women
– E-P combination to assess CHD / breast CA
– RR spine and hip fractures = 0.66
• Heart and Estrogen/progestin Replacement Study (HERS)- No reduction in fracture incidence
For relief of vasomotor symptoms
Not for prevention or treatment of osteoporosis .
SERMS- RALOXIFENE (EVISTA®)
Non-steroidal benzothiopene – binds Estrogen receptor, Inhibits bone resorption without stimulating endometrium
Multiple Outcomes of Raloxifene Evaluation (MORE)
- Studied 60 mg and 120 mg doses on patients with and without VCF(vertebral clinical fracture)
- 2.6% BMD compared to placebo
- 30% (prior VCF) and 50% (no prior VCF) reduction in VCF
- RR of DVT = 3
- Significant reduction in incidence of breast CA
Bazedoxifene binds to both ERs with high affinity
Agonist on skeletal tissue, with bone turnover reduced by 20–25% with doses of 20 or 40 mg daily
Antagonist on breast tissue and uterine tissue
Side effects are hot flashes
Selective Estrogen Receptor-ß Agonist, MF-101 ( 22 chinese herbal medicines)
MF-101-isolated active compounds, liquiritigen and chalcone, demonstrated selectivity for ER-ß
No effect on growth of breast cancer cells
No stimulation endometrium in Phase II trial
Effective in reducing the frequency and severity of hot flashes in postmenopausal women.
In order to confirm the safety and efficacy of MF-101, larger Phase III trials have been planned for 2009.
TSEC & SERMS
An appealing alternative strategy is the use of a tissue-specific estrogen complex (TSEC). TSECs combine an estrogen and a SERM, taking advantage of the tissue-specific anti-estrogenic properties of the SERM in order to counteract the effects of estrogen on the uterus and breast. This combination, therefore, requires no progestogen.
Pinkerton JV, Utian W, Constantine G, Olivier MD, Pickar J. SMART-2: A phase III study of the efficacy and safety of bazedoxifene/conjugated estrogens for treatment of menopausal vasomotor symptoms. Proceedings and abstract. Menopause . 2007;14(Suppl. 2):1081.
Poor intestinal absorption
N2 – containing
Patient should remain upright ,take with a glass of water
For prevention as well as treatment
Increases BMD by 8.8% in lumbar spine and 6% in fracture NOF
48% reduction in # NOF and spine fractures
Can be given for 5- 10 yrs or treatment free holidays can be givne.
DOSE:daily or weekly
Except – very elderly and poor renal function
PREVENTION : 5mg per day,35 mg /week
Treatment : 10 mg/day , 70 mg/week
Empty stomach consumption
Calcium to be taken after 4 hrs
Longest duration tried – upto 5 yrs
The Vertebral Efficacy with Risedronate
Therapy (VERT) Study
North American and Multinational Arms
Randomized, double-blind, placebo-controlled study of 2458 postmenopausal women c > 1 VCF
Treatment with 5mg/day for 3 years:
– incidence of new VCF by 41%
- BMD 5.4% vs. 1/1% (placebo)
Not recommended in patients with renal impairment
Inability to sit upright for 30 min.
• 32 amino acid polypeptide produced by the parafollicular “C” cells of the thyroid in response in plasma Calcium
• Binds to osteoclast cell receptor (-) effect)
• FDA approved for treatment but NOT prevention of
Women > 5yrs after menopause
Consider in women with estrogen-dependent neoplasm, H/o DVT, renal insufficiency, or active GI pathology
Nasal spray (preferred) and injectable forms
Miacalcin®: 200 IU qd
Prevent Recurrence of Osteoporotic Fracture Study (PROOF)
• 5-yr, multicenter, double-blind, randomized
study – 1255 patients
817 pts c 1-5 previous VCF
Nasal spray salmon calcitonin (100, 200, 400 IU)
• 36% reduction in VCF (33% for entire group)
Lumbar BMD 1.2% during only 1st yr
• Analgesic Effects
Analgesic for acute and chronic pain of VCF
Apparent by = 1 week
Mechanism likely a central effect (hypothalamus,PAG, dorsal horn)
Minimal: rhinitis, back/joint pain, HA
Antibodies in 20% PROOF patients
INJECTABLE – 100 IU/day s/c BIOCALCIN
NASAL SPRAY 200 IU /day MIACALCIN
Increases BMD by inhibiting osteoclast, decrease vertebral fractures
Good for pain in spinal fractures
PREVOS / SOTI / TROPOS
– Teriparatide = generic name
Synthetic teriparatide has been used in many clinical trials
Forteo is the recombinant DNA PTH 1-34 manufactured by Eli Lilly
Genetically engineered fragment of native PTH (84 amino acids)
FDA approved in US and Europe
• 24 month treatment period
– $ 600/month
A Recombinant DNA prep with all 84 amino acids (Preos) is in clinical trials
PTH (Forteo) Neer et al. (2001) NEJM 344(19), 1434-1441
• Landmark Placebo controlled, randomized trial of 1637
postmenopausal women with prior vertebral fracture
Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor- kB ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption , and increasing bone density
Dose of Denosumab
Denosumab given 60 mg subcutaneously twice yearly for 36 months associated with reduced risk of vertebral, nonvertebral and hip fractures in postmenopausal women with osteoporosis
( A ) The posture training support vest contains 680 g (1.5 pound) weights to remind the patient to extend their thoracic spine.
( B ) The Spinomed® brace consists of a back pad and strap system to strengthen the trunk muscle and improve posture.
( C ) Hip protectors contain padding over the trochanters to help absorb the impact of a fall
Sinaki M et al . (2002) Stronger back muscles reduce the incidence of vertebral fractures: a prospective 10 year follow-up of postmenopausal women. Bone 30: 836–841
05/01/10 dr.maninder AICOG2009 Improved back extensor strength correlate with decreased kyphosis and diminished vertebral fracture risk. Hip protectors don’t reduce incidence of hip fractures Van Schoor NM, Smit JH, Twisk JWR, et al. Prevention of hip fractures by external hip protectors: a randomized controlled trial. JAMA . 2003;289(15):1957–1962
Frailty and associated deconditioning;
Poor visual acuity;
Use of medications with that are sedating or compromise balance; and
Dangers in the environment, including loose rugs, lack of hand rails in the bathroom, etc.
05/01/10 dr.maninder AICOG2009
To Summarise”Drugs for prevention&treatment”
Estrogens/only in early menopause and premature menopause
Alendronate- 5-10mg daily,35-70 mg /weekly
Risendronate daily2.5-5mg/day or weekly
Ibandronate 150 mg monthly,3 monthly
Zolendronic acid yearly 3mg I/V over 10-15min
Calcitonin nasal spray 200 IU daily
Raloxifene 60mg daily,lipid friendly ,lowers LDL
Teriparatide s/c20 – 40 µg/day .can be given*18-24months
Strontium ranelate 2 gm/day
Osteoprotegrin 3 mg/kg s/c N-Telopeptide decreases in 5day
Tibolone(not FDA approved for osteoporosis)
Progesterone and growth hormones are being studied&also flourides
ePocrates. Computerized pharmacology and prescribing reference. updated daily. Available at: ePocrates.com Accessed September 19, 2008 .
05/01/10 dr.maninder AICOG2009
Lower Higher -2.5 BMD (T-score) Bisphosphonates Osteoporosis Therapy Algorithm Postmenopausal Women 05/01/10 Raloxifene PTH Calcitonin HRT HRT During Hot Flashes Post Vasomotor Symptoms Pre fracture Post Fracture Risk of Fracture AGE At Risk/Osteopenia Osteoporosis Severe Osteoporosis STAGE
OSTEOPOROSIS HIP FRACTURES 05/01/10
OSTEOPOROSIS HIP FRACTURES
High mortality &
morbidity by non-operative Treatment
OSTEOPOROSIS SPINE FRACTURES
Acute # :
NSAIDS & rest
Reduction in rate of bone loss
Reduction of rate of #
The real need in osteoporosis treatment is for additional anabolic agents
"Our success or failure in combating osteoporosis increasingly depends not so much on the drugs available to us but rather on our ability to engage our patients and ensure that they take the medications we prescribe