alcohol hiv art bone metabolism
Download
Skip this Video
Download Presentation
Alcohol, HIV, ART, & Bone Metabolism

Loading in 2 Seconds...

play fullscreen
1 / 42

Alcohol, HIV, ART, & Bone Metabolism - PowerPoint PPT Presentation


  • 135 Views
  • Uploaded on

Alcohol, HIV, ART, & Bone Metabolism. Robert W. Siggins 24 February 2012 [email protected] Metabolic Bone Disorders Overview. Origin in disrupted bone remodeling process Osteomalacia & rickets  bone softening from ↓ bone mineralization; Ca 3 (PO 4 ) 2 deficiency

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Alcohol, HIV, ART, & Bone Metabolism' - mariko


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
metabolic bone disorders overview
Metabolic Bone Disorders Overview
  • Origin in disrupted bone remodeling process
  • Osteomalacia & rickets  bone softening from ↓ bone mineralization; Ca3(PO4)2 deficiency
  • Osteoporosis ↑ loss total bone mass; resorption > formation
osteopenia and osteoporosis
Osteopenia and Osteoporosis
  • Osteopenia
    • Decreased bone
    • Not a diagnosis; Radiographic description
    • Etiology  Osteoporosis, osteomalacia, cancers, endocrine disorders
  • Osteoporosis
    • Decreased bone mass
    • Decreased cancellous (spongy) bone strength
osteoporosis
Osteoporosis
  • Porous bone
  • Poorly mineralized bone
  • Bone density
    • Normal bone
      • 833 mg/cm2
    • Osteopenic bone
      • 648 – 833 mg/cm2
    • Osteoporosis
      • < 648 mg/cm2
  • Diagnosis = 2.5 SD from normal female

Femoral Head

3 d micro ct healthy vs osteoporotic bone
3-D Micro CT:Healthy vs Osteoporotic Bone

84 year old Female

(w/ vertebral fracture)

52 year old Female

Borah et al Anat. Rec.(2001)

osteoporosis1
Osteoporosis
  • Potential causes
    • Decreased levels of estrogen and testosterone
    • Alcohol Abuse
    • HIV / HAART
    • Inadequate levels of vitamins D and C, or Mg++
    • Demonstrated by reduced bone mass / density and an imbalance of bone resorption and formation
  • Bone histology is usually normal but it lacks structural integrity
osteoporoses of long bones
Osteoporoses of Long Bones

Postmenopausal = cancellous bone; vertebrae, metaphyses; endocrtical surfaces of long bone

Alcoholic = decreased total remodeling of both cancellous and cortical (compact) bone

ca regulation
Ca++ Regulation

http://www.endocrinesurgery.net.au/parathyroidfunction/

normal bone remodeling
Normal Bone Remodeling
  • Osteoblasts “bone building” cells
  • They control bone remodeling by:
    • Laying down new bone
    • Secrete RANK ligand (RANKL) that controls osteoclasts “bone breaking” cells
  • Normally, bone formation and breakdown are balanced:
    • Replace damaged bone
    • Maintain amount & density of bone
bone growth
Bone Growth
  • Bone cells and bone marrow cells produce osteoprotegerin (OPG)  inhibited by PTH
    • Blocks RANKL
    • Prevents osteoclast development & function
    • Bone breakdown decreases
    • Bones grow
slide18

Osteocytes  50 cellular projections; extend throughout bone matrix; connect osteocytes to osteocytes & to cells at the bone surface  form the lacunocanalicular network

Nat med 17(10):1235, 2011

matrix embedded bm cells
Matrix Embedded BM Cells
  • Osteocytes
    • Floxed RANKL mouse crossed with osteocyte specific Cre mouse
    • No change in total bone RANKL mRNA or circulationg RANKL
    • >70% decrease in OC number

Nat med 17(10):1235, 2011

alcohol and bone metabolism
Alcohol and Bone Metabolism
  • Osteoblast #, osteoid synthesis, osteoid mineralization rate ↓ in human alcoholics compared to nonalcoholic controls; Impaired polyamine pathway (Klein and Carlos, 1995)
  • Cortical bone loss  decreased bone formation rate (BFR) (Hogan et al., 1997)
  • Young adult-to-adult rats  starting age of ethanol feeding increases, cancellous bone loss > cortical bone
  • Bone marrow in osteoporotic bone ↓ osteogenic cells, ↑ adipocytes (Burkhardt et al., 1987)

ACER 29(12):2077, 2005

alterations in the immuno skeletal interface drive bone destruction in hiv 1 transgenic rats

Alterations in the immuno-skeletal interface drive bone destruction in HIV-1 transgenic rats

Tatyana Vikulina, et. al.

PNAS 107(31):13848 2010

slide24

Bone Mineral Density

n = 4

n = 4

n = 6

Average ± SD, *P ≤ 0.05 by Mann-Whitney test

slide25

Longitudinal

trabecular

X-sectional

trabecular

Cortical

Scale bar = 1 mm

slide26

A. CTx = C-terminal telopeptide (n = 4)

B. Serum osteocalcin (n = 4)

TRAP = Tartrate resistant acid phosphatase

slide27

G. OCs / BS (n = 4)

H. OCs Surface / BS (n = 4)

Mineralized bone stains orange/pink (H & E Stain)

slide29

C. Role of TNFα in OCgenesis

D. OC precursors

E. Histogram = macrophages; Bar graph RT-qPCR for M-CSF

haart effects
HAART Effects
  • N(n)RTIs inhibit mitochondria 
    • Ox Stress?
    • Chronic lactic acidosis?
  • Protease Inhibitors 
    • Enhance OCgenesis and activity
    • Decrease OBgenesis and activity
  • Impaired Vit D metabolism 
    • Osteomalacia  Osteopenia

AIDS 23:1297-1310, 2009

slide37

Alcohol too!

AIDS 23:1297-1310, 2009

healing hematoma formation
Healing—Hematoma Formation

Blood vessels tear and bleedHematoma

HematomaFibrin meshwork

Inflammatory cell, influx, fibroblast ingrowth, and capillary bud formation

healing fibrous callus
Healing—Fibrous Callus

Infiltrating capillaries procallus

Fibroblasts (periosteum, endosteum, red marrow) fibrocartilaginous “glue”

2-3 weeks

healing bony callus
Healing—Bony Callus

Osteogenic cells (MSCs)  Osteoblasts

Osteoblasts  spongy bone trabeculae

Bony sheath covers fibrous callus

Spongy bone calcifies

3-4 weeks

to months

healing remodeling
Healing—Remodeling

Osteoclasts remove dead bone

Compact replaces spongy bone (fracture periphery)

Thickened area remains

ad