Osteoporosis

osteoporosis

What is osteoporosis?

Normal bone trabeculae

Bone trabeculae with osteoporosis

Impared bone strength -Low BMD -Poor bone quality Due to bone loss Increased fracture risk Graphic used with permission from the 2004 Surgenon General’s Report on Bone Health and Osteoporosis: What is Means To You

World Health Organization (WHO) guidelines for osteoporosis Peak Bone Mass T-Score Norma l Osteoporosis

Osteope nia 2.5

2.0

1.0

0

Osteoporosis epidemiology

millions

Total 210 millions in the world!

Principal sites of osteoporotic fractures

Lumbar spine and femoral neck are a major concern Hip fractures almost always require surgery and hospitalization. Spine fractures have serious consequences such as loss of height, severe back pain, deformity ,and spinal cord compression Hip Fractures will gain pain lasting 6 months About one of third patient if their got hip fractures they would lose physical performance and increasing mortality by 17% with in one year Spine fractures can lead to other complications

Bone Densitometry in Clinical Practice.BMJ.1995;310:1507-1510

Risk Factors (1)

Certain people are more likely to develop this disease than others. • Female • Thin and/or small frame • Advanced age • Family history of osteoporosis • Post menopause

Risk Factors(2) •

Anorexia nervosa or bulimia

•

Diet low in calcium

•

Use of certain medications

•

Low testosterone levels in men

•

An inactive lifestyle

•

Cigarette smoking

•

Excessive use of alcohol

•

Being white or Yellow

BMD Tests • • •

Can detect osteoporosis before a fracture occurs. Predicts your chances of fracturing in the future. Determines your rate of bone loss and monitors the effects of treatment.

How can you prevent osteoporosis

Follow the Food Guide Pyramid for Dietary Calcium Sources sunlight

Approved by FDA and SFDA

ibandronate

Ibandronate

Bisphosphonates •

Oral weekly – Alendronate (Fosamax) – Risedronate (Actonel)

•

Monthly oral – Ibandronate (Boniva)

•

Intravenous – Ibandronate (Bonviva)

Ibandronate

•

Newest licensed bisphosphonate

•

Good data for vertebral fracture reduction

•

Intermittent therapy – Oral monthly 150mg dose – Intravenous 3 monthly 2-3 mg dose

Dignosis and tratment path

What should a Bisphosphonate deliver for a patient? Efficacy -Reduction of vertebral fractures -Reduction of non-vertebral fractures -Reduction of fractures risk reduction - Fast onset of fracture risk reduction -Effectiveness in Randomized Controlled Studies and in “real life” Safety and tolerability -Reduction of turnover and increase in mineralization to optimal levels -Long term effectiveness -Gastrointestinal safe under real-life conditions

Intravenous ibandronate injections in postmenopausal women with osteoporosis: One-year results from the dosing intravenous administration study (DIVA) N= 1,395 women (ages 55-80 years) who were at least 5 years postmenopausal

5.0

5.1

4.8 3.8

L2-4 0

n=365 n=353 ２ mg/2mo3mg/3mo

n=377 2.5mg orally

ConclusionAs assessed by BMD, intravenous injections of ibandronate (2 mg every 2 months or 3 mg every 3 months) are at least as effective as the regimen of 2.5 mg orally daily, which has proven antifracture efficacy, and are well tolerated. Arthritis Rheum. 2006 Jun;54(6):1838-46

Clinical application Primary osteoporosis

Post menopausal osteoporosis

Osteoporosis in men Secondary osteoporosis

Corticosteroid-induced osteoporosis

Klinefelter’s syndrome

Bone loss

Kidney transplant Renal osteodystrophy

Change of BMD(%)

Efficacy and safety of ibandronate given by intravenous injection once every 3 months.

6 5 4 3 2 1 0 -1

5 2.8

-0.04 1mg iv (n = 261)

2mg iv (n = 131)

placebo(n=128)

N=520

After 1 year, ibandronate therapy produced substantial and dose-dependent increases in lumbar spine and hip BMD, lumbar spine BMD increased by 5.0% and 2.8% in the 2 and 1 mg groups, respectively, and decreased by 0.04% in the placebo group. Furthermore, total hip BMD increased by 2.9%, 2.2%, and 0.6%, respectively. 。 Bone. 2004 May;34(5):881-889

Oral ibandronate in postmenopausal osteoporotic women (dose finding)

Spine BMD(100%)

106

2.5mg 5.0mg 1.0mg

104 102

0.5mg 0.25mg

100

0

98

0

3

6

9

Months Bone. 1996 Nov;19(5):527-33

12

Three monthly intravenous injections of ibandronate in the treatment of postmenopausal osteoporosis. 6

5.2

BMD g/cm2

5 4

3.5

3

3.7

2.4

2 1 0

0.85 placebo 0.25mg

0.5mg

1mg

2mg

125 postmenopausal women (mean age, 64 years) with osteoporosis , (bone mineral density [BMD] < -2.5 SD T score) received a placebo or ibandronate (0.25, 0.5, 1, or 2 mg) every 3 months. All patients received 1 g calcium/day. BMD, in g/cm2 Am J Med 1997,Oct;103(4):298-307

Intravenous ibandronate injections given every three months: a new treatment option to prevent bone loss in postmenopausal women 5.00%

Ibandronate vs placebo P=0.0001

4.00% 3.00%

IB 2mg vs other groups, p<0.05 6.50 5.70

2.00%

1.30

1.00%

-0.70

0.00% ­1.00%

2mg

1mg

0.5mg

Placebo

N=629 PMO treatment for 1 year Ann Rhewn Dis 2003,62(10):969-925

Intravenous ibandronate in men with osteoporosis

Fourteen men with primary osteoporosis, mean age 57 ± 12 yr (range: 4073), received 2-mg ibandronate iv every 3 months over 2 yr. All got 1 g/day calcium and 880 UI/day vitamin D for 2 yr. BMD

P-value

Lumber Spine

6.7±1.5%

< 0.001

Trochanter

3.2±0.8%

< 0.001

Femoral neck

1.4±1.1%

>0.05

These results suggest that 3 months are a good interval between two doses of iv ibandronate, when 2 mg are given J Endocrinol Invest. 2003 Aug;26(8):728-32

Three-monthly ibandronate bolus injection offers favourable tolerability and sustained efficacy advantage over two years in established corticosteroid-induced osteoporosis

Method: N= 104 patients (49 men and 55 women) with established CIO (mean T-score <-2.5 S.D. (L2–L4) received daily calcium (500 mg) plus either 3-monthly i.v. ibandronate (2 mg) bolus injections or oral daily alfacalcidol (1 µg).

20

Ibandronate 15.5

alfacalcidol

16 11.9

12

7.6

8 4 0

4.7 2.2

lumbar spine 

1.3

femoral neck 

calcaneus 

Conclusions:Three-monthly i.v. ibandronate bolus injections are significantly superior to alfacalcidol in the treatment of CIO. lack of AEs and good compliance associated with intermittent i.v. ibandronate make it a potentially valuable alternative to oral bisphosphonate therapy for the treatment of CIO Rheumatology 2003; 42: 743-749

Intravenous ibandronate in men with osteoporosis: an open pilot study over 2 years. 14 men with primary osteoporosis, mean age 57 +/- 12 yr (range: 40-73), received 2-mg ibandronate iv every 3 months over 2 yr. ， All got 1 g/day calcium and 880 UI/day vitamin D

P-value

BMD lumbar spine 0.001

6.7±1.5%

p <

trochanter 0.001

3.2±0.8%

p <

femoral neck

1.4±1.1%

p >0.05

J Endocrinol Invest. 2003 Aug;26(8):728-32

Intermittent intravenous ibandronate injections reduce vertebral fracture risk in corticosteroid-induced osteoporosis: results from a long-term comparative study

ibandronate

alfacalcidol

p–value

lumbar spine L2-L4

13.3%

2.6%

p <0.001

femoral neck

5.2%

1.9%

p<0.001

16.5%

6.7%

p<0.001

new vertebral fractures rates

8.6%

22.8%

p=0.043

pain relieve

86.2%

49.1%

p<0.001

calcaneus

N=115

intermittent i.v. ibandronate (2mg/3mon )injections are efficacious, welltolerated, and convenient, and promise to offer physicians an important therapeutic advance in the management of osteoporosis. Osteoporos Int. 2003 Oct;14(10):801-7

Effective and rapid treatment of painful localized transient osteoporosis (bone marrow edema) with intravenous ibandronate. Bacground:Localized transient osteoporosis (LTO; bone marrow edema syndrome) is a rare disorder of generally unknown etiology that is characterized by acute onset of disabling bone pain. Treatment options are currently limited and largely ineffective Methods:N=12 patients with LTO, ibandronate was administered as an initial 4-mg i.v. dose with a second, optional injection of 2 mg at 3 months. 1, 2, 3, and 6 months using a visual analog scale (VAS) of 1-10, and BMD was measured at baseline and 6 months Results: Seven patients had achieved complete pain ; BMD (lumber) had increased by 4.0% Conclusion:Ibandronate injection affords advantages over currently available oral and i.v. bisphosphonates and thus offers a promising therapeutic advance in the treatment of LTO

Osteoporos Int (2005) 16: 2063–2068

Effect of Ibandronate on Bone Loss and Renal Function after Kidney Transplantation 2.7

4.00 0.5

2.00 0.00 -2.00

-0.9

-4.00 -6.00 -8.00

-4 -6.50

lumbar spine femoral neck midfemoral shaft

-7.7

-10.00 placebo

ibandronate

J Am Soc Nephrol 12:1530-7

The effects of three-month intravenous ibandronate on bone mineral density and bone remodeling in Klinefelter's syndrome The aim of this study was to evaluate the effects of a 2-year treatment with intravenous ibandronate (2 mg every 3 months) and calcium (1000 mg daily) on bone mineral density (BMD)

N=14 Bone. 2003 Oct;33(4):589-96

Treatment of reduced bone density with ibandronate in dialysis patients Patients (n=16) with end-stage renal disease (ESRD) and regular hemodialysis schedules were recruited , Patients received ibandronate 2 mg every 4 weeks for 48 weeks

0 weeks

48 Weeks

CaHA

88.94 ±31.68 mg/ml

93.51 ± 35.36 mg/ml

T-scores

-3.08 +/- 1.11

-2.78 +/- 1.27

（ p=0.032 ） (p<0.01)

Conclusion:In patients with renal osteodystrophy and ESRD, ibandronate significantly increased BMD and decreased bone turnover

J Nephrol. 2008 Jul-Aug;21(4):510-6

Therapy of hypercalcemia with ibandronate in case of acute renal failure we report the case of a female patient, suffering from primary hyperparathyroidism with severe hypercalcaemia and calcium levels up to 6 mmol/l, who developed acute renal failure. We treated the patient with forced diuresis and repeated infusions of ibandronate (5 x 6 mg ibandronate). Even if lowering the serum levels of calcium only for a short time after each application, yet we could improve renal function by these means. Only after performing a parathyroidectomy, we could see a sustained decline of calcium levels. This case report supports the results of other publications, that have reported the missing nephrotoxic effect of ibandronate compared to other bisphosphonates. Internist (Berl). 2006 Mar;47(3):293-6

Local peroperative treatment with a bisphosphonate improves the fixation of total knee prostheses: a randomized, double-blind radiostereometric study of 50 patients This is a double-blind, randomized study of 50 patients using RSA with maximal total point motion (MTPM) as primary effect variable. 1 mg ibandronate (1 mL) or 1 mL saline was applied to the tibial bone surface 1 min before cementation. RSA examination was done on the first postoperative day, and at 6, 12, and 24 months. 0.5

RSA

0.4 0.3 IB saline

0.2 0.1 0

6months

12months

24months

CONCLUSIONS: This is the first study to show improvement of prosthesis fixation by local pharmacological treatment in humans. The treatment appears to be safe, cheap, and easy to perform. Acta Orthop. 2007 Dec;78(6):795-9. Links

Treatment persistence research

60.00%

56.60%

Persistence

50.00% 38.40%

40.00%

p < 0.0001

30.00% 20.00% 10.00% 0.00%

ibandronate 306/541

alendronate 198/513 Int J Clin Pract. 2006 Aug;60(8):896-905

Treatment persistence research 80.00% 70.00%

71.40%

patient's preferrance

60.00% 50.00% 40.00% 28.60%

30.00% 20.00% 10.00% 0.00%

ibandronate

alendronate Clin Ther. 2006 Apr;28(4):475-90

Patient prefreence for once-monthly over weekly bisphosphonate treatment

No Prefer

n=350

6.9%

P<0.0001 Prefer once-weekly 27.4% Prefer once-monthly 65.7%

Joint Bone Spine 2008;75(3):303-310

The association between compliance and persistence with bisphosphonate therapy and fracture risk: a review.

10.70%

12.00% 10.00%

N= 35,537

8.50%

8.00% 6.00% risk of fracture

4.00% 2.00% 0.00%

MPR>80%

MPR<80% p<0.001

Medication Possession Ratio =MPR BMC Musculoskelet Disord.2007 Sep 26;8:97