# Presentation: 174875

## Slide 1

## ASBMR Membership:An Overview

**Membership Affiliation**

- Total Membership: 	3,597*

- *Total as of September 2002

**Membership  **
**Location**

## ASBMR Mission

**	****	**
**	****	****The mission of the ASBMR is to promote excellence in bone and mineral research, fostering integration of clinical and basic science, and facilitating the translation of our science to health care and clinical practice. **
**	**

## ASBMR Position Statement on the WHI Findings

**ASBMR MEMBERSHIP**

## ASBMR Position Statement

**HRT clearly prevents clinical osteoporotic fractures in postmenopausal women even those who are relatively healthy**
**HRT increased the rate of breast cancer, myocardial infarction, stroke and VTE in postmenopausal women in WHI**
**The absolute increase in rates for these events  in WHI was relatively small; yet there were 19 more events caused than events saved/10,000 person-years;**
**Postmenopausal women at risk for osteoporosis and considering long term therapy, should discuss with their provider treatment options and consider the safest risk/benefit ratio as determined by the evidence**

## Osteoporosis

**Common, serious morbidity/mortality**
**vertebral and non-vertebral fractures**
**Pain, disability**
**What should we offer women??**
**Many treatments now available:**
**Ca/VitD,**
**HRT,SERMS,**
**Bisphosphonates**
**nCT**
**How? Evidence review+ values/ preferences considered versus global recommendations**

## Osteoporosis Advisory Group (ORAG)

**Evidence Based Research Group Composed of:**
**Clinical Trial Specialists-McMaster**
**Methodologists-McMaster/Ottawa**
**Experts in Metabolic Bone Disease-9 members ASBMR**
**	**
**Three years of data analysis for all RCPTs in Osteoporosis**
**	**
**	****End point: A series of manuscripts on “Therapies for Postmenopausal Osteoporosis” were published in *****Endocrine Reviews *****in June 2002.**
**	****Three ASBMR Presidents participated in ORAG:**
**	****John Bilezikian**
**	****Robert Marcus**
**	****Clifford Rosen**

## Therapies for Osteoporosis:The Evidence

- Estrogen/Estrogen-Progestin

## RR of Non-Vertebral Fracture with HRT

**RR of Non-Vertebral Fracture with HRT**

- '

- '

- '

- '

- '

- '

- '

- '

- Greenspan 1998 (0.70 (0.22, 2.22)

- Komulainen 1997 0.40 (0.16, 0.99)

-  Wilalawansa 1998  1.00 (0.07, 14.79)

- Hulley 1998  0.90 (0.69, 1.19)

- Hosking 1998  0.98 ( 0.29, 3.34))

- Alexandersen 1999  0.31 ( 0.03, 2.76)

- WHI  2002 0.68 ( 0.46, 0.99)

- Pooled Estimate 0.78 (0.64, 0.96)

- 0.01

- 0.1

- 1

- 10

- 100

- Relative Risk (95% CI)

**Favours HRT             Favours Control**

- (N =2763)

- (N =193)

- (N =612)

- (N =36)

- (N =232)

- (N =50)

- (N =16608)

- (N =20494)

## Slide 10

## *

**Pooled Estimate 0.78 (0.64, 0.96): ****HRT**

*****

**Favors Rx****	****	****Favors Placebo**

- N=20,494

**Pooled Estimate  0.51 (0.38 to 0.69):Alendronate**

*****

- N=3722

**Pooled Estimate 0.68 (0.54 to 0.85):Residronate**

*****

- N= 3330

**Pooled Estimate  0.77 (0.57 to 1.04):Vit D**

*****

- N= 6333

**Pooled Estimate    0.91 (0.78 to 1.06):Raloxifene**

*****

- N=7848

-             **0.5                   0.75              1.0                 1.25            1.50**

**Evidence Based Reviews**
**Non-Vertebral Fractures**

- Endocrine
- Reviews
- June 2002

## Relative Risk  with 95% CI for Vertebral Fractures for Doses 

**of 5mg or Greater of Alendronate**

- Adami and Hoskings trials not included in figure due to low vertebral fracture incidence.

- '

- '

- '

- '

- '

- '

- '

- '

- '

- '

- McClung 0.34 (0.04 to 3.25)

- Pooled Prevention Estimate 0.45(0.06 to 3.15)

- Bone 0.68 ( 0.21 to 2.18)

- Chesnut 0.25 (0.03 to 2.34)

- Liberman (USA) 0.52 ( 0.24 to 1.15)

- Liberman (Int) 0.52 ( 0.20 to 1.34)

- Black 0.53 (0.41 to 0.69)

- Cummings 0.51 ( 0.31 to 0.84)

- Pooled Treatment Estimate 0.53 (0.43 to 0.65)

- Pooled Estimate   0.52 (0.43 to 0.65)

- 0.01

- 0.1

- 1

- 10

*** *****Prevention Trials**

**Favours Alendronate    Favours Control**

- (n = 355)

- (n = 1355)

- (n =  184)

- (n = 157)

- (n = 478)

- (n = 516)

- (n = 2027)

- (n = 4432 )

- (n = 8005 )

- (n = 9360)

**Treatment Trials**

## Early treatment may be appropriate

- Baseline risk of fracture from alendronate   RCTs over 2 year period
- non-osteoporotic     AbsFrxRate  	NNTs
- vertebral                      0.12%	           1,790
- non-vertebral               2.54%                  80
- osteoporotic
- vertebral 		       2.88% 		      72
- non-vertebral               6.85%    	      24

##  Benefits for Women at Risk for Osteoporosisas Established by Evidence Based Reviews 

- Drugs that reduce vertebral fractures
*vitamin D, HRT, raloxifene, risedronate, alendronate*
- Drugs that reduce non-vertebral fractures
*HRT (1/4-1/3 RRR), risedronate (1/3 RRR), alendronate (1/2 RRR)*

## Values and Preferences in Women with Osteoporosis

**High **value:fracture reduction – early treatment
- 		no uncertainty: alendronate,residronate
**High** value: reducing fractures, no inconvenience
- Alendronate, risedronate, _??_calcitonin
**High** value: acutely reduce postmenopausal symptoms
- HRT
**High** value on “natural” treatment, low cost
- Calcium and vitamin D
- 	**High** value on preventing breast cancer:
- 		-raloxifene

## Summary

**Several therapies are now available to treat or prevent osteoporosis**
**Therapies should be considered on evidence based data from RPCTs**
**Values and Preferences of the patient must be considered in the light of available evidence to allow women and providers to make the appropriate choice**