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Source:. Conclusion Slides. Review:. Reviewer Memo:. Slide Modified:. Memo:. Source:. Bone Quality. Review:. Bone quality is an integral component of bone strength Maintaining or restoring bone architecture is required for optimal bone quality

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conclusion slides

Source:

Conclusion Slides

Review:

Reviewer Memo:

Slide Modified:

Memo:

bone quality

Source:

Bone Quality

Review:

  • Bone quality is an integral component of bone strength
  • Maintaining or restoring bone architecture is required for optimal bone quality
  • Bone turnover rate affects the degree of mineralization of bone
  • Optimal collagen/mineral matrix properties contribute to bone quality

Reviewer Memo:

Slide Modified:

Memo:

bone quality1

Source:

Bone Quality

Review:

  • Bone quality is an integral component of bone strength
  • Maintaining or restoring bone architecture is required for optimal bone quality
  • Bone turnover rate affects the degree of mineralization of bone

Reviewer Memo:

Slide Modified:

Memo:

raloxifene summary of bone quality effects

Source:

Raloxifene: Summary of Bone Quality Effects

Review:

  • Changes in BMD explain only a small proportion of vertebral fracture risk reduction shown with raloxifene
  • Raloxifene reduces bone turnover to the premenopausal range allowing
    • Repair of microdamage
    • Preservation of heterogeneous mineral distribution
    • A modest increase in mineralization

Reviewer Memo:

Slide Modified:

Memo:

possible contributing factors to the antifracture efficacy of antiresorptives

Source:

Possible Contributing Factors to the Antifracture Efficacy of Antiresorptives

Review:

  • Increase bone mineral density
  • Decrease bone turnover
  • Preserve bone microarchitecture
    • Decrease number of remodeling sites
    • Maintain trabecular thickness and connectivity
    • Decrease number of trabecular perforations

Reviewer Memo:

Slide Modified:

Memo:

bone quality raloxifene

Source:

Bone Quality Raloxifene

Review:

  • Biochemical markers and bone turnover significantly reduced to premenopausal range
  • Normal bone turnover allows adequate repair of microdamage
  • No adverse effect on bone histology

Reviewer Memo:

Slide Modified:

Memo:

bone quality raloxifene1

Source:

Bone Quality Raloxifene

Review:

  • Histomorphometry
    • No woven bone
    • No marrow fibrosis
    • No mineralization defect
    • No cellular toxicity (light microscopy)
    • Normal histologic appearance

Reviewer Memo:

Weinstein RS, et al. J Bone Miner Res. 14:S279; 1999

Prestwood KM, et al. J Clin Endocrinol Metab. 85:2197-2202; 2000

Ott SM, et al. J Bone Miner Res. 17:341-348; 2002

Slide Modified:

Memo:

bone quality raloxifene2

Source:

Bone Quality Raloxifene

Review:

  • No adverse effects on bone histology
  • Changes in BMD explain only a small proportion of vertebral fracture risk reduction
  • Reduces bone turnover to the normal premenopausal range
  • A moderate increase in mineralization and preservation of heterogeneous mineral distribution
  • Long-term efficacy with sustained fracture reduction in the fourth year of treatment
  • Favorable effects on femoral neck geometry

Reviewer Memo:

Slide Modified:

Memo:

slide9

Source:

Bone Quality ConclusionsTeriparatide

Review:

  • Architecture
    • Increase trabecular thickness and connectivity
    • Increase cortical thickness and improves cortical geometry
    • Favorable effects on femoral neck geometry
  • Turnover
    • Increase formation on quiescent (neutral) surface
    • Increase in formation is greater than resorption (positive bone balance)
    • Transient increase in cortical porosity without impact on bone strength
  • Damage Accumulation
    • Forms new bone
    • Increased bone turnover reduces damage accumulation

Reviewer Memo:

Slide Modified:

Memo:

slide10

Source:

Bone Quality ConclusionsTeriparatide

Review:

  • Architecture
    • Increase trabecular thickness and connectivity
    • Increase cortical thickness and improves cortical geometry
    • Favorable effects on femoral neck geometry
  • Turnover
    • Increase formation on quiescent (neutral) surface
    • Increase in formation is greater than resorption (positive bone balance)
    • Transient increase in cortical porosity without impact on bone strength

Reviewer Memo:

Slide Modified:

Memo:

slide11

Decrease

perforations

Decrease

resorption

cavities

Maintain

Plate-like structure

Decrease

stress risers

Maintain

Horizontal struts

Preserve

strength

Source:

Turnover Reduction

Within normal physiologic range

Review:

Reviewer Memo:

Slide Modified:

Memo:

slide12

Prolonged secondary

mineralization

Insufficient fatigue

damage repair

Excessive mineralization

+ homogeneous bone

Microcrack

accumulation

Microcrack

propagation

Increased

fragility

Source:

Excessive Turnover Reduction

Below normal physiologic range

Review:

Reviewer Memo:

?

Slide Modified:

Memo:

slide13

Normal

Osteoporosis

Severe Osteoporosis

Courtesy Dr. A. Boyde

Source:

Review:

Reviewer Memo:

Slide Modified:

Memo:

slide14

Insufficient turnover

    • Accumulation of microdamage
    • Increased brittleness due to excessive mineralization
  • Excessive turnover
    • Increase in stress risers (weak zones)
    • Increase in perforations
    • Loss of connectivity

Physiological Range

Source:

What Is the Optimal Reduction in Bone Turnover for an AntiresorptiveDrug?

Review:

Reviewer Memo:

Bone Strength

Bone Turnover

Sourced from Weinstein RS, J Bone Miner Res 15 621-625, 2000

Slide Modified:

Memo:

summary of bone quality effects of raloxifene and teriparatide

Source:

Summary of Bone Quality Effects of Raloxifene and Teriparatide

Review:

Reviewer Memo:

June 2004

Slide Modified:

Memo:

the assessment of bone quality advances in technology

Source:

The Assessment of Bone Quality- Advances in Technology

Review:

Reviewer Memo:

Slide Modified:

Memo:

cadaver vertebrae fem vs bct

10

ORS 2004

8

6

4

2

0

0

50

100

150

200

250

Source:

Cadaver Vertebrae: FEM vs. BCT

Experiments

QCT

BCT

Review:

Reviewer Memo:

2

r

=0.65, SE=1.11 kN

Strength (kN)

Compressive strength (kN)

Crawford et al, Bone 2003

0 50 100 150 200 250

QCT-BMD x A

(mg/mm)

Model Strength (kN)

QCT-BMD xA (mg/mm)

min

June 2004

min

Slide Modified:

Memo:

virtual bone biopsy

Source:

Virtual Bone Biopsy

Review:

  • Wrist detection coils
  • Microscopy-specific MRI scanner software enhancements
  • 3D image processing and analysis

Reviewer Memo:

Slide Modified:

Memo:

supplemental slides

Source:

Supplemental Slides

Review:

Reviewer Memo:

Slide Modified:

Memo:

the effect of antiresorptive therapy on fracture healing study protocol

Source:

The Effect of Antiresorptive Therapy on Fracture Healing Study Protocol

Review:

  • Female OVX rats (n=140)
  • Five study groups
      • Sham control
      • OVX placebo control
      • OVX + estrogen
      • OVX + raloxifene
      • OVX + alendronate
  • Objective: To evaluate the effect of antiresorptives on fracture healing.

Reviewer Memo:

Cao Y et al. J Bone Miner Res 17:2237-46; 2002

Slide Modified:

Memo:

the effect of antiresorptive therapy on fracture healing external callus formation

Source:

The Effect of Antiresorptive Therapy on Fracture Healing External Callus Formation

Review:

  • 6 Weeks
    • Callus formation
    • Fracture visible

Reviewer Memo:

  • 16 Weeks
    • OVX Fracture line dissapeared
    • ALN fracture line still visible
    • Callus width largest in ALN group
    • Fracture repair was delayed with ALN treatment

Reproduced with permission from Cao Y et al. J Bone Miner Res 17:2237-46, 2002

Slide Modified:

Memo:

the effect of antiresorptive therapy on fracture healing photomicrographs of the callus

Source:

The Effect of Antiresorptive Therapy on Fracture Healing Photomicrographs of the Callus

Review:

Reviewer Memo:

Sham OVX EE2 RLX ALN

Reproduced with permission from Cao Y et al. J Bone Miner Res 17:2237-46, 2002

June 2004

Slide Modified:

Memo:

urinary markers of bone resorption

Source:

Urinary Markers of Bone Resorption

Review:

Marker Abbreviation

Hydroxyproline HYP

Pyridinoline PYD

Deoxypyridinoline DPD

N-terminal cross-linking telopeptide of type I collagen NTX

C-terminal cross-linking telopeptide of type I collagen CTX

Reviewer Memo:

Delmas PD. J Bone Miner Res 16:2370; 2001

Slide Modified:

Memo:

serum markers of bone turnover

Source:

Serum Markers of Bone Turnover

Review:

Abbreviation

Formation

Bone alkaline phosphatase ALP (BSAP)

Osteocalcin OC

Procollagen type I C-propeptide PICP

Procollagen type I N-propeptide PINP

Resorption

N-terminal cross-linking telopeptide of type I collagen NTX

C-terminal cross-linking telopeptide of type I collagen CTX

Tartrate-resistant acid phosphatase TRAP

Reviewer Memo:

Delmas PD. J Bone Miner Res 16:2370, 2001

Slide Modified:

Memo:

effect of size on areal bmd

Source:

Effect of Size on Areal BMD

Review:

BMC

Area

BMD

1

1

1

1

1

1

2

2

Reviewer Memo:

8

4

2

2

3

3

27

9

3

3

“True” Value = 1 g/cm3

Adapted from Carter DR, et al. J Bone Miner Res 1992

Slide Modified:

Memo:

local buckling

Source:

Local Buckling

Review:

Reviewer Memo:

Slide Modified:

Memo: