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

- - - 0
2.5 2.0 1.0
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

5.1 4.8
5.0
3.8

L2-4

n=365
0
n=353 n=377
２ mg/2mo3mg/3mo 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
 Efficacy and safety of ibandronate given by intravenous
injection once every 3 months.

Change of BMD(%)
6 5
5
4
2.8
3
2
1 -0.04
0
1mg iv (n = 261) 2mg iv (n = 131) placebo(n=128)
-1

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)

106
2.5mg
Spine BMD(100%)

104 5.0mg
1.0mg
102 0.5mg
0.25mg
100 0

98
0 3 6 9 12
Months

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

Three monthly intravenous injections of ibandronate
in the treatment of postmenopausal osteoporosis.
6
5.2
5

4 3.7
3.5
BMD g/cm2

3
2.4
2

0.85
1

0 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%
IB 2mg vs other groups, p<0.05
3.00% 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: 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 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

20
Method: N= 104 patients (49 Ibandronate
15.5
men and 55 women) with alfacalcidol
16
established CIO (mean T-score
11.9
<-2.5 S.D. (L2–L4) received
12
daily calcium (500 mg) plus
7.6
either 3-monthly i.v.
ibandronate (2 mg) bolus 8
4.7
injections or oral daily 2.2
alfacalcidol (1 µg). 4 1.3

0
lumbar spine  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

BMD P-value
lumbar spine 6.7±1.5% p <
0.001
trochanter 3.2±0.8% p <
0.001
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
calcaneus 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

N=115
intermittent i.v. ibandronate (2mg/3mon )injections are efficacious, well-
tolerated, 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
2.00 0.5
lumbar spine
0.00
-2.00 -0.9 femoral neck
-4.00 -4
midfemoral shaft
-6.00
-6.50
-8.00 -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 （ p=0.032 ）

(p<0.01)
T-scores -3.08 +/- 1.11 -2.78 +/- 1.27

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

0.4

0.3
RSA

IB
0.2 saline

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%

40.00% 38.40%
p < 0.0001
30.00%

20.00%

10.00%

0.00%
ibandronate alendronate
306/541 198/513

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

 Treatment persistence research

80.00%
71.40%
70.00% patient's preferrance

60.00%
50.00%
40.00%
30.00% 28.60%

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
6.9% n=350
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.

12.00% 10.70%
N= 35,537
10.00% 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