Biochemical markers in the diagnosis and monitoring of osteoporosis

1
Biochemical markers in the diagnosis and
monitoring of osteoporosis

• Karl Schweitzer
• Jefferson Medical College, MSII
• Advisor Dr. William Z. Borer

http//www.lab.anhb.uwa.edu
8th Annual Research Symposium in Pathology April
27-28th, 2006
2
Osteoporosis Overview

• A metabolic bone disease
• Affects gt 75 million people in Europe, Japan, and
  U.S. (WHO, Prev. Manage., 2003)
• Increased risk of bone fractures with associated
  morbidity and mortality

Vertebral body from young adult
Vertebral body from osteoporosis patient
http//www.lab.anhb.uwa.edu
3
Osteoporosis - WHO definition

• Based on T score from bone-mineral density (BMD)
  measurement using dual-energy x-ray
  absorptiometry (DEXA scan)
• Osteoporosis gt 2.5 SD below mean
• Osteopenia 1 - 2.5 SD below mean

4
Treatment of Osteoporosis

• Calcium and vitamin D supplements
• Bisphosphonates (alendronate1,2, risedronate3-5)
• Calcitonin
• Selective estrogen receptor modulators (SERMS)
• Recombinant PTH
• Others

5
1? vs. 2? Osteoporosis

• 1? OP - related to normal aging and decreased
  gonadal function
• 2? OP - accelerated bone loss due to other
  chronic conditions

Endocrine/Metabolic - acromegaly, anorexia
nervosa, athletic amenorrhea, hemochromatosis,
hyperadrenocorticism, hyperparathyroidism,
thyrotoxicosis Collagen/Genetic Disorders -
Ehlers-Danlos syndrome, glycogen storage
diseases, homocystinuria, hypophosphatasia,
Marfan syndrome, osteogenesis imperfecta Medicatio
ns - cyclosporine, excess thyroid hormone,
glucocorticoid tx, methotrexate, phenobarbital,
phenothiazines, phenytoin, prolonged heparin
tx Nutritional - alcoholism, calcium deficiency,
chronic liver disease, gastric operations,
malabsorption syndromes, vitamin D deficiency
6
Study of Lab Workup to Identify 2º OP
Contributors6

• Proposed the following screening protocol
• - 24 hr urine Ca2
• - serum Ca2
• - serum PTH
• - (serum thyrotropin)
• Conclusion Could identify 2º causes of OP in 86
  of women with disorders _at_ approx. cost 75/pt

7
OP Biomarkers - Overview

• Derived from cortical and trabecular bone
• Rapid measurement, non-invasive, inexpensive,
  proven use in therapeutic monitoring
• Major disadvantage most are non-specific and
  levels are affected by many factors

8
Markers of Bone Formation

• Measured in serum or plasma
• Products of active osteoblasts
• Examples . . .
• - Alkaline phosphatase
• - Osteocalcin7
• - Procollagen type I propeptides8

9
Markers of Bone Resorption

• Degradation products of bone collagen
• Urinary hydroxyproline and hydroxylysine-glycoside
  s
• Urinary hydroxypyridium collagen crosslinks9-11

10
Future Use of Biochemical Markers

• Which patients are suffering from decreasing bone
  mass?
• Is a particular patient at a high risk for
  fracture?
• What treatment would be best in a particular
  patient?
• What is the therapeutic response level?

11
Conclusion

• Bone markers non-invasive, inexpensive, allow
  for frequent assessment
• Lack of established guidelines for clinical
  application in OP monitoring and diagnosis
• An area of ongoing research and development . . .

12
Thanks to . . .

• Dr. William Borer
• TJU Department of Pathology, Anatomy, and Cell
  Biology
• References and slides available upon request