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Effects of Bisphosphonates and PTH on Fracture Healing and Spine Fusion “Subtrochanteric Fractures” Joseph M. Lane, MD Hospital for Special Surgery NEW YORK. Joseph M. Lane, MD. Source:. Review:. Does have a financial interest or relationship with the manufacturers of products or services:

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slide1

Effects of Bisphosphonates and PTH on Fracture Healing and Spine Fusion “Subtrochanteric Fractures”Joseph M. Lane, MDHospital for Special SurgeryNEW YORK

joseph m lane md
Joseph M. Lane, MD

Source:

Review:

Does have a financial interest or relationship

with the manufacturers of products or

services:

  • Consulting Fees: Amgen, Arthrocare, Biomimetics, D’Fine, Innovative Clinical Solutions, Kuros Biosurgery AG, Osteotech, Orthovita, Soteira, Zelos, Zimmer
  • Speakers’ Bureaus: Eli Lilly, Novartis, Orthovita, Proctor and Gamble, Roche, Sonofi - Aventis

Presentation will not include discussion of off

label or investigational use of products or

treatments

Reviewer Memo:

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

the goal increased bone strength

Source:

The Goal: Increased Bone Strength

Review:

NIH Consensus Statement 20001

Bone

Strength

Bone

Quality

Bone

Mineral

Density

Reviewer Memo:

and

Architecture/Geometry

Bone Remodeling

Damage Accumulation

Mineralization of Matrix

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

risk of vertebral fracture
Risk of Vertebral Fracture

Source:

Review:

5x greater with prior vertebral fracture

Vertebral fracture

2x risk of hip fracture

Fracture more fractures

Reviewer Memo:

(Nevitt 1999)

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

metabolic bone disease workup for osteopenia
Metabolic Bone DiseaseWorkup For Osteopenia

Source:

Review:

Bone Marrow CBC

Sed Rate

Immunoelectro-Phoresis

Endocrinopathy Hyper Thyroid, Hyper PTH, Cushings, Juvenile Diabetes

Osteomalacia- Calcium, Phos, Alk-Ptase, PTH

25 Hydroxy Vit D

Osteoporosis – High vs. Low

Turnover NTX

Reviewer Memo:

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

agents against osteoporosis
Agents Against Osteoporosis

Source:

Review:

Antiresorption

(Experimental)

Estrogen Calcitonin

Bisphosphonates

Serms

Bone Stimulation

PTH

Strontium Renalate

Reviewer Memo:

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

bisphosphonates
Bisphosphonates

Source:

Review:

Bone Mass (Spine/Hip)

Fracture Risk (Vertebra/Long Bones)

= Fracture Healing (animal/patients)

Reviewer Memo:

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

animal studies
Animal Studies

Source:

Review:

Remodeling

Healing

Callus

=Biomechanics

Reviewer Memo:

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

clinical trials bisphosphonates in fracture healing
Clinical Trials – Bisphosphonates in Fracture Healing

Source:

Review:

Colles’ Fracture (Alendronate)

Tibia Shaft/Ankle (Alendronate)

Hip fractures (Zoledronic Acid)

↑ Bone Mass (DXA)

No Difference in Clinical Union

↓ Secondary Fracture

↓ Mortality

(Van der Poest JBMR 200, 2002)

(Lyles NEJM 2007)

Reviewer Memo:

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

pth 1 34 anabolic agent
PTH (1-34) Anabolic Agent

Source:

Review:

Bone mass

All fractures

Enhances fracture healing

Spine fusion

In animal studies

Reviewer Memo:

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

intermittent pth 1 34 rat femoral fracture
Intermittent PTH (1-34)Rat Femoral Fracture

Source:

Review:

Bone Mineral Content

Bone Mineral Density

Bone Mineral Strength

Sustained Anabolic Effect

Large Cartilaginous Callus

No Chondrocyte Differentiation Delay

Alkhary

Einhorn JBJS 2005

Nakazawa - Bone 2005

Reviewer Memo:

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

fracture healing pth vs bisphosphonates
Fracture Healing: PTH vs. Bisphosphonates

Source:

Review:

Animal

Reviewer Memo:

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

alendronate
Alendronate

Source:

Review:

Long term effect unkown

Theoretically dose with time

Keep collagen breakdown products low

Reviewer Memo:

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

prolonged bisphosphonates
Prolonged Bisphosphonates

Source:

Review:

Turnover

Microfracture

Frozen Bone

Brittle Fracture

(PAK)

Reviewer Memo:

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

background
Background

Source:

Review:

  • Animal studies have linked bisphosphonate use to microdamage accumulation
  • Case series have identified atypical fractures
    • Odvina et al J Clin Endocrinol Metab 2005;90:1294
    • Goh et al JBJS Br 2007;89:349
    • Kwek et al Injury 2008;39:224

Reviewer Memo:

  • Neviaser, et al J Orthop Trauma (2008)

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

methods
Methods

Source:

Review:

  • Retrospective case-control study 2000-2007
    • Cases: postmenopausal women with subtrochanteric/shaft (ST/S) fractures
        • Low energy mechanism
    • Controls: postmenopausal women with intertrochanteric (IT) or femoral neck (FN) fractures
    • Matched by age, race and BMI
  • X-ray confirmation of fracture type
  • Exclusion of any identifiable secondary causes of bone loss

Reviewer Memo:

1. NIH Consensus Development Panel on Osteoporosis 2000. JAMA. 2001;285:785-795.

Slide Modified:

Memo:

rate of alendronate use
Rate of Alendronate Use
  • Subtrochanteric/Shaft
    • 2 patients on 10 mg alendronate daily
    • Remaining 13 on 70 mg every week
  • Hip Fracture Controls
    • 2 patients on 35 mg alendronate every week
    • 1 took etidronate for 5 years then 70 mg alendronate for 2 years
    • 1 patient was on 35 mg risedronate every week and was included in this group
    • Remaining 5 on alendronate 70 mg every week
  • OR 4.68, 95% CI (1.83-11.89)
simple with thick cortices fracture
Simple With Thick Cortices Fracture

83 year old female with a 9 year history of alendronate use

77 year old female with a 5 year history of alendronate use

st s fracture
ST/S Fracture

83 year old female with no history of alendronate use

60 year old female with no history of alendronate use

simple with thick cortices fracture1
Simple With Thick Cortices Fracture
  • X-ray Pattern Definition: simple transverse or oblique with cortical thickening and beaking of the cortex on one side
  • OR 15.33, 95% CI (3.06-76.90)
distribution by fracture type
Distribution by Fracture Type
  • Kruskal Wallis one-way variance analysis on the duration of alendronate use in patients in all three groups yielded P=0.001
  • Subtroch/shaft vs. Intertroch P=0.01
  • Subtroch/shaft vs. Fem Neck P=0.001
  • Fem Neck vs. Intertroch P=0.3

*1 pt on risedronate, **1 pt on etidronate for 5 years, then alendronate for 2

conclusions
Conclusions

Long-term bisphosphonate use decreases risk of hip

fractures at IT/FN (94%) regions but may increase at ST/S

regions (6%)

A small subgroup of patients may be more susceptible to

the effects of prolonged therapy

Further studies are needed to confirm whether prolonged

use increases the risk of ST/S fractures and to

characterize this subgroup of patients

osteoporosis treatment comparison
Osteoporosis Treatment Comparison

Bone

FormationRemodeling

Normal Fx Healing ↑↑ ↑

Bisphosphonates ↓ ↓↓

PTH ↑↑ ↑

question
Question

Mechanism

Treatment

slide40

Mechanism

Stress fracture

3 months pain

Local ↑ diameter

slide41
Bisphosphonates given to normal diaphyseal

bone

increased microdamage

collagen aging >> fiber failure

>> loss of toughness >> low energy

spontaneous fracture

Working Hypothesis

slide42

Treatment

Stop bisphosphonate

Correct Ca/VIT D

Consider PTH 1-34 (anabolic)

slide43
Patient with thigh pain

History – bisphosphonate

X-Ray → MRI / bone scan

slide44

To Prevent Abnormal Bone Consider a Bone Holiday

Old FxNew Fx

No Pain Pain

↓ ↓

Anabolic Anabolic

Consider nailing

osteoporosis new fracture treatment
Osteoporosis New Fracture Treatment

Calcium (Citrate) [1,000 mg Ca]

Vitamin D3 [2 – 6,000 units/day]

Short half-life bisphosphonate/lower dose

PTH → bisphosponate

Bone turnover determines TX: right in the

middle

fracture on bisphosphonate
Fracture on Bisphosphonate

Rule out secondary cause

Stop bisphosphoate

Correct calcium/vitamin D

Consider PTH

clinical studies
Clinical Studies

Clinical characterization of fracture healing

Evaluation of bone quality

Histology - Doty

Micro-Ct - Mayer-Kuckuk

F-TIR - Boskey

hss osteoporosis team
MD/PhD

Adele Boskey

Richard Bockman

Edward Dicarlo

Steven Doty

Steve Goldring

Dean Lorich

Linda Russell

Robert Schneider

Dave Zackson

FELLOWS

Jaimo Ahn

Padhraig O’Laughlin

Philipp Mayer-Kuckuk

Alana Serota

Aasis Unnanuntana

STUDENTS/RESIDENTS

Charles Chang

Lily Bogunovich

Brian Gladnick

Flo Edobor-Osula

Brett Lenart

Dennis Merideth

Andy Neviaser

Barbara Schreck

RN’S/NP’S

Janet Curtin

Patricia Donnelly

Diana Lapiano

Lisa Shindle

HSS Osteoporosis Team
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