Effects of Bisphosphonates and PTH on Fracture Healing and Spine Fusion “Subtrochanteric Fractures...
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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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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 Spine Fusion “Subtrochanteric Fractures”

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: Spine Fusion “Subtrochanteric Fractures”

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 Spine Fusion “Subtrochanteric Fractures”

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 Disease Spine Fusion “Subtrochanteric Fractures”Workup 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 Spine Fusion “Subtrochanteric Fractures”

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 Spine Fusion “Subtrochanteric Fractures”

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 Spine Fusion “Subtrochanteric Fractures”

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 Spine Fusion “Subtrochanteric Fractures”

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 Spine Fusion “Subtrochanteric Fractures”

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) Spine Fusion “Subtrochanteric Fractures”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: Spine Fusion “Subtrochanteric Fractures”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 Spine Fusion “Subtrochanteric Fractures”

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:


Subtrochanteric fracture
Subtrochanteric Fracture Spine Fusion “Subtrochanteric Fractures”


Prolonged bisphosphonates
Prolonged Bisphosphonates Spine Fusion “Subtrochanteric Fractures”

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 Spine Fusion “Subtrochanteric Fractures”

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 Spine Fusion “Subtrochanteric Fractures”

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 Spine Fusion “Subtrochanteric Fractures”

    • 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 Spine Fusion “Subtrochanteric Fractures”

    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 Spine Fusion “Subtrochanteric Fractures”

    83 year old female with no history of alendronate use

    60 year old female with no history of alendronate use


    Not for duplication Spine Fusion “Subtrochanteric Fractures”

    24


    Not for duplication Spine Fusion “Subtrochanteric Fractures”

    6


    Not for duplication Spine Fusion “Subtrochanteric Fractures”

    20


    Not for duplication Spine Fusion “Subtrochanteric Fractures”

    31


    Not for duplication Spine Fusion “Subtrochanteric Fractures”

    2


    Bis 24

    Not for duplication Spine Fusion “Subtrochanteric Fractures”

    Bis-24


    Bis 6

    Not for duplication Spine Fusion “Subtrochanteric Fractures”

    Bis-6


    No bis 20

    Not for duplication Spine Fusion “Subtrochanteric Fractures”

    No Bis-20


    Bis 31

    Not for duplication Spine Fusion “Subtrochanteric Fractures”

    Bis-31


    No bis 2

    Not for duplication Spine Fusion “Subtrochanteric Fractures”

    No Bis-2


    Simple with thick cortices fracture1
    Simple With Thick Cortices Fracture Spine Fusion “Subtrochanteric Fractures”

    • 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)


    Pattern vs absence of pattern
    Pattern vs. Absence of Pattern Spine Fusion “Subtrochanteric Fractures”


    Distribution by fracture type
    Distribution by Fracture Type Spine Fusion “Subtrochanteric Fractures”

    • 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 Spine Fusion “Subtrochanteric Fractures”

    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 Spine Fusion “Subtrochanteric Fractures”

    Bone

    FormationRemodeling

    Normal Fx Healing ↑↑ ↑

    Bisphosphonates ↓ ↓↓

    PTH ↑↑ ↑


    Question
    Question Spine Fusion “Subtrochanteric Fractures”

    Mechanism

    Treatment


    Mechanism Spine Fusion “Subtrochanteric Fractures”

    Stress fracture

    3 months pain

    Local ↑ diameter


    Bisphosphonates given to normal diaphyseal Spine Fusion “Subtrochanteric Fractures”

    bone

    increased microdamage

    collagen aging >> fiber failure

    >> loss of toughness >> low energy

    spontaneous fracture

    Working Hypothesis


    Treatment Spine Fusion “Subtrochanteric Fractures”

    Stop bisphosphonate

    Correct Ca/VIT D

    Consider PTH 1-34 (anabolic)


    Patient with thigh pain Spine Fusion “Subtrochanteric Fractures”

    History – bisphosphonate

    X-Ray → MRI / bone scan


    To Prevent Abnormal Bone Consider a Bone Holiday Spine Fusion “Subtrochanteric Fractures”

    Old FxNew Fx

    No Pain Pain

    ↓ ↓

    Anabolic Anabolic

    Consider nailing


    Osteoporosis new fracture treatment
    Osteoporosis New Fracture Treatment Spine Fusion “Subtrochanteric Fractures”

    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 Spine Fusion “Subtrochanteric Fractures”

    Rule out secondary cause

    Stop bisphosphoate

    Correct calcium/vitamin D

    Consider PTH


    Clinical studies
    Clinical Studies Spine Fusion “Subtrochanteric Fractures”

    Clinical characterization of fracture healing

    Evaluation of bone quality

    Histology - Doty

    Micro-Ct - Mayer-Kuckuk

    F-TIR - Boskey


    Hss osteoporosis team

    MD/PhD Spine Fusion “Subtrochanteric Fractures”

    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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